Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer
Abstract
:1. Introduction
2. Crosstalk between the Immune System and Microbiomes on Homeostatic Regulation in GI Cancer
3. Influence of Pathogens and Role of Immune Cells in GI Cancer
3.1. Influence of Microbiomes on GI Cancer
3.2. Influence of Virali Infection in GI Cancers
3.3. Paracrine Effect of Fibroblasts on GI Cancer
3.4. Drivers of Innate Immunity and GI Cancer
3.4.1. NK Cells
3.4.2. Dendritic Cells
3.4.3. Macrophages
3.4.4. Myeloid-Derived Suppressor Cells
3.5. Drivers of Adaptive Immunity and GI Cancer
3.5.1. T Lymphocytes
3.5.2. B Lymphocytes
3.5.3. NKT Cells
3.5.4. Regulatory T Cells
4. Immune Landscape Determinants and Predictors in GI Cancer
5. Progress and Current Immunotherapeutic Approaches in GI Cancers
5.1. Adoptive T-Cell Therapy
5.1.1. Chimeric Antigen Receptor T Cells
5.1.2. Tumor-Infiltrating Lymphocytes
5.1.3. CIK
5.2. Bispecific T-Cell Engagers
5.3. Cancer Vaccines
5.4. Checkpoint Inhibitors
5.5. NK Cell-Based Therapies
5.6. Stroma-Targeted Therapies
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Vesely, M.D.; Schreiber, R.D. Cancer Immunoediting: Antigens, Mechanisms, and Implications to Cancer Immunotherapy. Ann. N. Y. Acad. Sci. 2013, 1284, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Zumwalt, T.J.; Goel, A. Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives. Curr. Colorectal Cancer Rep. 2015, 11, 125–140. [Google Scholar] [CrossRef] [PubMed]
- Han, E.Q.; Li, X.L.; Wang, C.R.; Li, T.F.; Han, S.Y. Chimeric Antigen Receptor-Engineered T Cells for Cancer Immunotherapy: Progress and Challenges. J. Hematol. Oncol. 2013, 6, 47. [Google Scholar] [CrossRef] [PubMed]
- Shi, L.; Chen, S.; Yang, L.; Li, Y. The Role of PD-1 and PD-L1 in T-Cell Immune Suppression in Patients with Hematological Malignancies. J. Hematol. Oncol. 2013, 6, 74. [Google Scholar] [CrossRef] [PubMed]
- Hazama, S.; Tamada, K.; Yamaguchi, Y.; Kawakami, Y.; Nagano, H. Current Status of Immunotherapy against Gastrointestinal Cancers and Its Biomarkers: Perspective for Precision Immunotherapy. Ann. Gastroenterol. Surg. 2018, 2, 289–303. [Google Scholar] [CrossRef] [PubMed]
- Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; et al. A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing. Nature 2010, 464, 59–65. [Google Scholar] [CrossRef] [PubMed]
- Tremaroli, V.; Backhed, F. Functional Interactions between the Gut Microbiota and Host Metabolism. Nature 2012, 489, 242–249. [Google Scholar] [CrossRef] [PubMed]
- Pennisi, E. Biomedicine. Cancer Therapies Use a Little Help from Microbial Friends. Science 2013, 342, 921. [Google Scholar] [CrossRef] [PubMed]
- Bouskra, D.; Brezillon, C.; Berard, M.; Werts, C.; Varona, R.; Boneca, I.G.; Eberl, G. Lymphoid Tissue Genesis Induced by Commensals through NOD1 Regulates Intestinal Homeostasis. Nature 2008, 456, 507–510. [Google Scholar] [CrossRef] [PubMed]
- Diaz Heijtz, R.; Wang, S.; Anuar, F.; Qian, Y.; Bjorkholm, B.; Samuelsson, A.; Hibberd, M.L.; Forssberg, H.; Pettersson, S. Normal Gut Microbiota Modulates Brain Development and Behavior. Proc. Natl. Acad. Sci. USA 2011, 108, 3047–3052. [Google Scholar] [CrossRef] [PubMed]
- Smith, C.L.; Dickinson, P.; Forster, T.; Craigon, M.; Ross, A.; Khondoker, M.R.; France, R.; Ivens, A.; Lynn, D.J.; Orme, J.; et al. Identification of a Human Neonatal Immune-Metabolic Network Associated with Bacterial Infection. Nat. Commun. 2014, 5, 4649. [Google Scholar] [CrossRef] [PubMed]
- Dominguez-Bello, M.G.; Godoy-Vitorino, F.; Knight, R.; Blaser, M.J. Role of the Microbiome in Human Development. Gut 2019, 68, 1108–1114. [Google Scholar] [CrossRef] [PubMed]
- Saus, E.; Iraola-Guzman, S.; Willis, J.R.; Brunet-Vega, A.; Gabaldon, T. Microbiome and Colorectal Cancer: Roles in Carcinogenesis and Clinical Potential. Mol. Aspects Med. 2019. [Google Scholar] [CrossRef] [PubMed]
- Weng, M.T.; Chiu, Y.T.; Wei, P.Y.; Chiang, C.W.; Fang, H.L.; Wei, S.C. Microbiota and Gastrointestinal Cancer. J. Formos. Med. Assoc. 2019, 118, S32–S41. [Google Scholar] [CrossRef] [PubMed]
- Dickson, I. Microbiome Promotes Pancreatic Cancer. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 328. [Google Scholar] [CrossRef] [PubMed]
- Pushalkar, S.; Hundeyin, M.; Daley, D.; Zambirinis, C.P.; Kurz, E.; Mishra, A.; Mohan, N.; Aykut, B.; Usyk, M.; Torres, L.E.; et al. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018, 8, 403–416. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zambirinis, C.P.; Pushalkar, S.; Saxena, D.; Miller, G. Pancreatic Cancer, Inflammation, and Microbiome. Cancer J. 2014, 20, 195–202. [Google Scholar] [CrossRef] [Green Version]
- Sun, J.; Furio, L.; Mecheri, R.; van der Does, A.M.; Lundeberg, E.; Saveanu, L.; Chen, Y.; van Endert, P.; Agerberth, B.; Diana, J. Pancreatic Beta-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota. Immunity 2015, 43, 304–317. [Google Scholar] [CrossRef]
- Jenne, C.N.; Kubes, P. Immune Surveillance by the Liver. Nat. Immunol. 2013, 14, 996–1006. [Google Scholar] [CrossRef]
- Liu, Y.; Seto, N.L.; Carmona-Rivera, C.; Kaplan, M.J. Accelerated Model of Lupus Autoimmunity and Vasculopathy Driven by Toll-Like Receptor 7/9 Imbalance. Lupus Sci. Med. 2018, 5, e000259. [Google Scholar] [CrossRef]
- Huang, L.R.; Wohlleber, D.; Reisinger, F.; Jenne, C.N.; Cheng, R.L.; Abdullah, Z.; Schildberg, F.A.; Odenthal, M.; Dienes, H.P.; van Rooijen, N.; et al. Intrahepatic Myeloid-Cell Aggregates Enable Local Proliferation of CD8(+) T Cells and Successful Immunotherapy against Chronic Viral Liver Infection. Nat. Immunol. 2013, 14, 574–583. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Meng, Z.; Jiang, M.; Zhang, E.; Trippler, M.; Broering, R.; Bucchi, A.; Krux, F.; Dittmer, U.; Yang, D.; et al. Toll-Like Receptor-Induced Innate Immune Responses in Non-Parenchymal Liver Cells Are Cell Type-Specific. Immunology 2010, 129, 363–374. [Google Scholar] [CrossRef] [PubMed]
- Bronte, V.; Wang, M.; Overwijk, W.W.; Surman, D.R.; Pericle, F.; Rosenberg, S.A.; Restifo, N.P. Apoptotic Death of CD8+ T Lymphocytes after Immunization: Induction of a Suppressive Population of Mac-1+/Gr-1+ Cells. J. Immunol. 1998, 161, 5313–5320. [Google Scholar] [PubMed]
- Mazzoni, A.; Bronte, V.; Visintin, A.; Spitzer, J.H.; Apolloni, E.; Serafini, P.; Zanovello, P.; Segal, D.M. Myeloid Suppressor Lines Inhibit T Cell Responses by an No-Dependent Mechanism. J. Immunol. 2002, 168, 689–695. [Google Scholar] [CrossRef] [PubMed]
- Notas, G.; Kisseleva, T.; Brenner, D. Nk and NKT Cells in Liver Injury and Fibrosis. Clin. Immunol. 2009, 130, 16–26. [Google Scholar] [CrossRef] [PubMed]
- Robinson, M.W.; Harmon, C.; O’Farrelly, C. Liver Immunology and Its Role in Inflammation and Homeostasis. Cell Mol. Immunol. 2016, 13, 267–276. [Google Scholar] [CrossRef] [PubMed]
- Signoretti, M.; Roggiolani, R.; Stornello, C.; Delle Fave, G.; Capurso, G. Gut Microbiota and Pancreatic Diseases. Minerva Gastroenterol Dietol. 2017, 63, 399–410. [Google Scholar]
- Dejea, C.M.; Fathi, P.; Craig, J.M.; Boleij, A.; Taddese, R.; Geis, A.L.; Wu, X.; DeStefano Shields, C.E.; Hechenbleikner, E.M.; Huso, D.L.; et al. Patients with Familial Adenomatous Polyposis Harbor Colonic Biofilms Containing Tumorigenic Bacteria. Science 2018, 359, 592–597. [Google Scholar] [CrossRef]
- Fan, X.; Alekseyenko, A.V.; Wu, J.; Peters, B.A.; Jacobs, E.J.; Gapstur, S.M.; Purdue, M.P.; Abnet, C.C.; Stolzenberg-Solomon, R.; Miller, G.; et al. Human Oral Microbiome and Prospective Risk for Pancreatic Cancer: A Population-Based Nested Case-Control Study. Gut 2018, 67, 120–127. [Google Scholar] [CrossRef]
- Olsen, I.; Yamazaki, K. Can Oral Bacteria Affect the Microbiome of the Gut? J. Oral. Microbiol. 2019, 11, 1586422. [Google Scholar] [CrossRef]
- Shaik-Dasthagirisaheb, Y.B.; Huang, N.; Weinberg, E.O.; Shen, S.S.; Genco, C.A.; Gibson, F.C., 3rd. Aging and Contribution of MYD88 and TRIF to Expression of TLR Pathway-Associated Genes Following Stimulation with Porphyromonas Gingivalis. J. Periodontal Res. 2015, 50, 89–102. [Google Scholar] [CrossRef] [PubMed]
- Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; et al. Tumor-Associated B7-H1 Promotes T-Cell Apoptosis: A Potential Mechanism of Immune Evasion. Nat. Med. 2002, 8, 793–800. [Google Scholar] [CrossRef]
- Nielsen, S.R.; Quaranta, V.; Linford, A.; Emeagi, P.; Rainer, C.; Santos, A.; Ireland, L.; Sakai, T.; Sakai, K.; Kim, Y.S.; et al. Macrophage-Secreted Granulin Supports Pancreatic Cancer Metastasis by Inducing Liver Fibrosis. Nat. Cell Biol. 2016, 18, 549–560. [Google Scholar] [CrossRef]
- Wang, L.; Zhu, R.; Huang, Z.; Li, H.; Zhu, H. Lipopolysaccharide-Induced Toll-Like Receptor 4 Signaling in Cancer Cells Promotes Cell Survival and Proliferation in Hepatocellular Carcinoma. Dig. Dis. Sci. 2013, 58, 2223–2236. [Google Scholar] [CrossRef] [PubMed]
- Akira, S.; Takeda, K. Toll-Like Receptor Signalling. Nat. Rev. Immunol. 2004, 4, 499–511. [Google Scholar] [CrossRef]
- Naugler, W.E.; Sakurai, T.; Kim, S.; Maeda, S.; Kim, K.; Elsharkawy, A.M.; Karin, M. Gender Disparity in Liver Cancer Due to Sex Differences in MYD88-Dependent IL-6 Production. Science 2007, 317, 121–124. [Google Scholar] [CrossRef]
- Gagniere, J.; Raisch, J.; Veziant, J.; Barnich, N.; Bonnet, R.; Buc, E.; Bringer, M.A.; Pezet, D.; Bonnet, M. Gut Microbiota Imbalance and Colorectal Cancer. World J. Gastroenterol 2016, 22, 501–518. [Google Scholar] [CrossRef] [PubMed]
- Baxter, N.T.; Zackular, J.P.; Chen, G.Y.; Schloss, P.D. Structure of the Gut Microbiome Following Colonization with Human Feces Determines Colonic Tumor Burden. Microbiome 2014, 2, 20. [Google Scholar] [CrossRef]
- Kostic, A.D.; Chun, E.; Robertson, L.; Glickman, J.N.; Gallini, C.A.; Michaud, M.; Clancy, T.E.; Chung, D.C.; Lochhead, P.; Hold, G.L.; et al. Fusobacterium Nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. Cell Host Microbe 2013, 14, 207–215. [Google Scholar] [CrossRef]
- Ryz, N.R.; Patterson, S.J.; Zhang, Y.; Ma, C.; Huang, T.; Bhinder, G.; Wu, X.; Chan, J.; Glesby, A.; Sham, H.P.; et al. Active Vitamin D (1,25-Dihydroxyvitamin D3) Increases Host Susceptibility to Citrobacter Rodentium by Suppressing Mucosal Th17 Responses. Am. J. Physiol. Gastrointest Liver Physiol. 2012, 303, G1299–G1311. [Google Scholar] [CrossRef]
- Loddo, I.; Romano, C. Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis. Front. Immunol. 2015, 6, 551. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, S.; Rhee, K.J.; Albesiano, E.; Rabizadeh, S.; Wu, X.; Yen, H.R.; Huso, D.L.; Brancati, F.L.; Wick, E.; McAllister, F.; et al. A Human Colonic Commensal Promotes Colon Tumorigenesis Via Activation of T Helper Type 17 T Cell Responses. Nat. Med. 2009, 15, 1016–1022. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.H.; Hu, L.L.; Gonzalez-Navajas, J.; Seo, G.S.; Shen, C.; Brick, J.; Herdman, S.; Varki, N.; Corr, M.; Lee, J.; et al. ERK Activation Drives Intestinal Tumorigenesis in APC(Min/+) Mice. Nat. Med. 2010, 16, 665–670. [Google Scholar] [CrossRef] [PubMed]
- Dejea, C.M.; Wick, E.C.; Hechenbleikner, E.M.; White, J.R.; Mark Welch, J.L.; Rossetti, B.J.; Peterson, S.N.; Snesrud, E.C.; Borisy, G.G.; Lazarev, M.; et al. Microbiota Organization Is a Distinct Feature of Proximal Colorectal Cancers. Proc. Natl. Acad. Sci. USA 2014, 111, 18321–18326. [Google Scholar] [CrossRef] [PubMed]
- Hold, G.L.; Allen-Vercoe, E. Gut Microbial Biofilm Composition and Organisation Holds the Key to CRC. Nat. Rev. Gastroenterol Hepatol. 2019, 16, 329–330. [Google Scholar] [CrossRef] [PubMed]
- Tomkovich, S.; Dejea, C.M.; Winglee, K.; Drewes, J.L.; Chung, L.; Housseau, F.; Pope, J.L.; Gauthier, J.; Sun, X.; Muhlbauer, M.; et al. Human Colon Mucosal Biofilms from Healthy or Colon Cancer Hosts Are Carcinogenic. J. Clin. Invest. 2019, 130, 1699–1712. [Google Scholar] [CrossRef]
- Liao, R.; Sun, J.; Wu, H.; Yi, Y.; Wang, J.X.; He, H.W.; Cai, X.Y.; Zhou, J.; Cheng, Y.F.; Fan, J.; et al. High Expression of IL-17 and IL-17RE Associate with Poor Prognosis of Hepatocellular Carcinoma. J. Exp. Clin. Cancer Res. 2013, 32, 3. [Google Scholar] [CrossRef]
- Oh, J.K.; Weiderpass, E. Infection and Cancer: Global Distribution and Burden of Diseases. Ann. Glob Health 2014, 80, 384–392. [Google Scholar] [CrossRef]
- Liu, C.J.; Chu, Y.T.; Shau, W.Y.; Kuo, R.N.; Chen, P.J.; Lai, M.S. Treatment of Patients with Dual Hepatitis C and B by Peginterferon Alpha and Ribavirin Reduced Risk of Hepatocellular Carcinoma and Mortality. Gut 2014, 63, 506–514. [Google Scholar] [CrossRef]
- Fiorino, S.; Lorenzini, S.; Masetti, M.; Deleonardi, G.; Grondona, A.G.; Silvestri, T.; Chili, E.; Del Prete, P.; Bacchi-Reggiani, L.; Cuppini, A.; et al. Hepatitis B and C Virus Infections as Possible Risk Factor for Pancreatic Adenocarcinoma. Med. Hypotheses 2012, 79, 678–697. [Google Scholar] [CrossRef]
- Tomasiewicz, K.; Modrzewska, R.; Lyczak, A.; Krawczuk, G. TT Virus Infection and Pancreatic Cancer: Relationship or Accidental Coexistence. World J. Gastroenterol 2005, 11, 2847–2849. [Google Scholar] [CrossRef] [PubMed]
- Pelizzer, T.; Dias, C.P.; Poeta, J.; Torriani, T.; Roncada, C. Colorectal Cancer Prevalence Linked to Human Papillomavirus: A Systematic Review with Meta-Analysis. Rev. Bras. Epidemiol. 2016, 19, 791–802. [Google Scholar] [CrossRef] [PubMed]
- Jarzynski, A.; Zajac, P.; Zebrowski, R.; Boguszewska, A.; Polz-Dacewicz, M. Occurrence of Bk Virus and Human Papilloma Virus in Colorectal Cancer. Ann. Agric. Environ. Med. 2017, 24, 440–445. [Google Scholar] [CrossRef] [PubMed]
- Mjelle, R.; Sjursen, W.; Thommesen, L.; Saetrom, P.; Hofsli, E. Small Rna Expression from Viruses, Bacteria and Human Mirnas in Colon Cancer Tissue and Its Association with Microsatellite Instability and Tumor Location. BMC Cancer 2019, 19, 161. [Google Scholar] [CrossRef] [PubMed]
- Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-Related Inflammation. Nature 2008, 454, 436–444. [Google Scholar] [CrossRef] [PubMed]
- Zur Hausen, H. The Search for Infectious Causes of Human Cancers: Where and Why. Virology 2009, 392, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Szabo, G.; Petrasek, J. Inflammasome Activation and Function in Liver Disease. Nat. Rev. Gastroenterol Hepatol. 2015, 12, 387–400. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Mao, R.; Yang, J. NF-Kappab and Stat3 Signaling Pathways Collaboratively Link Inflammation to Cancer. Protein Cell 2013, 4, 176–185. [Google Scholar] [CrossRef]
- Naugler, W.E.; Karin, M. NF-Kappab and Cancer-Identifying Targets and Mechanisms. Curr. Opin. Genet. Dev. 2008, 18, 19–26. [Google Scholar] [CrossRef]
- Wu, W.K.; Sung, J.J.; Lee, C.W.; Yu, J.; Cho, C.H. Cyclooxygenase-2 in Tumorigenesis of Gastrointestinal Cancers: An Update on the Molecular Mechanisms. Cancer Lett. 2010, 295, 7–16. [Google Scholar] [CrossRef]
- He, G.; Yu, G.Y.; Temkin, V.; Ogata, H.; Kuntzen, C.; Sakurai, T.; Sieghart, W.; Peck-Radosavljevic, M.; Leffert, H.L.; Karin, M. Hepatocyte Ikkbeta/NF-Kappab Inhibits Tumor Promotion and Progression by Preventing Oxidative Stress-Driven Stat3 Activation. Cancer Cell 2010, 17, 286–297. [Google Scholar] [CrossRef] [PubMed]
- Greten, F.R.; Weber, C.K.; Greten, T.F.; Schneider, G.; Wagner, M.; Adler, G.; Schmid, R.M. Stat3 and Nf-Kappab Activation Prevents Apoptosis in Pancreatic Carcinogenesis. Gastroenterology 2002, 123, 2052–2063. [Google Scholar] [CrossRef] [PubMed]
- Chung, S.S.; Wu, Y.; Okobi, Q.; Adekoya, D.; Atefi, M.; Clarke, O.; Dutta, P.; Vadgama, J.V. Proinflammatory Cytokines IL-6 and TNF-Alpha Increased Telomerase Activity through NF-Kappa-b/STAT1/STAT3 Activation, and Withaferin a Inhibited the Signaling in Colorectal Cancer Cells. Mediators Inflamm. 2017, 2017, 5958429. [Google Scholar] [CrossRef] [PubMed]
- Sunami, Y.; Ringelhan, M.; Kokai, E.; Lu, M.; O’Connor, T.; Lorentzen, A.; Weber, A.; Rodewald, A.K.; Mullhaupt, B.; Terracciano, L.; et al. Canonical NF-Kappa-b Signaling in Hepatocytes Acts as a Tumor-Suppressor in Hepatitis B Virus Surface Antigen-Driven Hepatocellular Carcinoma by Controlling the Unfolded Protein Response. Hepatology 2016, 63, 1592–1607. [Google Scholar] [CrossRef] [PubMed]
- Knolle, P.A.; Thimme, R. Hepatic Immune Regulation and Its Involvement in Viral Hepatitis Infection. Gastroenterology 2014, 146, 1193–1207. [Google Scholar] [CrossRef]
- Larrubia, J.R.; Lokhande, M.U.; Garcia-Garzon, S.; Miquel, J.; Gonzalez-Praetorius, A.; Parra-Cid, T.; Sanz-de-Villalobos, E. Persistent Hepatitis C Virus (Hcv) Infection Impairs HCV-Specific Cytotoxic T Cell Reactivity through Mcl-1/Bim Imbalance Due to CD127 Down-Regulation. J. Viral Hepat. 2013, 20, 85–94. [Google Scholar] [CrossRef] [PubMed]
- Wieland, D.; Kemming, J.; Schuch, A.; Emmerich, F.; Knolle, P.; Neumann-Haefelin, C.; Held, W.; Zehn, D.; Hofmann, M.; Thimme, R. Tcf1(+) Hepatitis C Virus-Specific CD8(+) T Cells Are Maintained after Cessation of Chronic Antigen Stimulation. Nat. Commun. 2017, 8, 15050. [Google Scholar] [CrossRef] [PubMed]
- Barber, D.L.; Wherry, E.J.; Masopust, D.; Zhu, B.; Allison, J.P.; Sharpe, A.H.; Freeman, G.J.; Ahmed, R. Restoring Function in Exhausted CD8 T Cells During Chronic Viral Infection. Nature 2006, 439, 682–687. [Google Scholar] [CrossRef]
- Khan, O.; Giles, J.R.; McDonald, S.; Manne, S.; Ngiow, S.F.; Patel, K.P.; Werner, M.T.; Huang, A.C.; Alexander, K.A.; Wu, J.E.; et al. Tox Transcriptionally and Epigenetically Programs CD8(+) T Cell Exhaustion. Nature 2019, 571, 211–218. [Google Scholar] [CrossRef]
- Schietinger, A.; Philip, M.; Krisnawan, V.E.; Chiu, E.Y.; Delrow, J.J.; Basom, R.S.; Lauer, P.; Brockstedt, D.G.; Knoblaugh, S.E.; Hammerling, G.J.; et al. Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early During Tumorigenesis. Immunity 2016, 45, 389–401. [Google Scholar] [CrossRef]
- Miller, B.C.; Sen, D.R.; Al Abosy, R.; Bi, K.; Virkud, Y.V.; LaFleur, M.W.; Yates, K.B.; Lako, A.; Felt, K.; Naik, G.S.; et al. Subsets of Exhausted CD8(+) T Cells Differentially Mediate Tumor Control and Respond to Checkpoint Blockade. Nat. Immunol. 2019, 20, 326–336. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.G.; Zheng, D.H.; Shi, M.; Xu, X.M. T Cell Dysfunction in Chronic Hepatitis B Infection and Liver Cancer: Evidence from Transcriptome Analysis. J. Med. Genet. 2019, 56, 22–28. [Google Scholar] [CrossRef] [PubMed]
- Paley, M.A.; Kroy, D.C.; Odorizzi, P.M.; Johnnidis, J.B.; Dolfi, D.V.; Barnett, B.E.; Bikoff, E.K.; Robertson, E.J.; Lauer, G.M.; Reiner, S.L.; et al. Progenitor and Terminal Subsets of CD8+ T Cells Cooperate to Contain Chronic Viral Infection. Science 2012, 338, 1220–1225. [Google Scholar] [CrossRef] [PubMed]
- Horton, B.L.; Williams, J.B.; Cabanov, A.; Spranger, S.; Gajewski, T.F. Intratumoral CD8(+) T-Cell Apoptosis Is a Major Component of T-Cell Dysfunction and Impedes Antitumor Immunity. Cancer Immunol. Res. 2018, 6, 14–24. [Google Scholar] [CrossRef] [PubMed]
- Kalluri, R. The Biology and Function of Fibroblasts in Cancer. Nat. Rev. Cancer 2016, 16, 582–598. [Google Scholar] [CrossRef]
- Orimo, A.; Gupta, P.B.; Sgroi, D.C.; Arenzana-Seisdedos, F.; Delaunay, T.; Naeem, R.; Carey, V.J.; Richardson, A.L.; Weinberg, R.A. Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion. Cell 2005, 121, 335–348. [Google Scholar] [CrossRef] [PubMed]
- Quante, M.; Tu, S.P.; Tomita, H.; Gonda, T.; Wang, S.S.; Takashi, S.; Baik, G.H.; Shibata, W.; Diprete, B.; Betz, K.S.; et al. Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth. Cancer Cell 2011, 19, 257–272. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Wang, J.; Asahina, K. Mesothelial Cells Give Rise to Hepatic Stellate Cells and Myofibroblasts via Mesothelial-Mesenchymal Transition in Liver Injury. Proc. Natl. Acad. Sci. USA 2013, 110, 2324–2329. [Google Scholar] [CrossRef]
- Su, S.; Chen, J.; Yao, H.; Liu, J.; Yu, S.; Lao, L.; Wang, M.; Luo, M.; Xing, Y.; Chen, F.; et al. CD10(+)GPR77(+) Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness. Cell 2018, 172, 841–856. [Google Scholar] [CrossRef]
- Ozdemir, B.C.; Pentcheva-Hoang, T.; Carstens, J.L.; Zheng, X.; Wu, C.C.; Simpson, T.R.; Laklai, H.; Sugimoto, H.; Kahlert, C.; Novitskiy, S.V.; et al. Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival. Cancer Cell 2014, 25, 719–734. [Google Scholar] [CrossRef] [Green Version]
- Lo, A.; Li, C.P.; Buza, E.L.; Blomberg, R.; Govindaraju, P.; Avery, D.; Monslow, J.; Hsiao, M.; Pure, E. Fibroblast Activation Protein Augments Progression and Metastasis of Pancreatic Ductal Adenocarcinoma. JCI Insight 2017, 2. [Google Scholar] [CrossRef] [PubMed]
- Santos, A.M.; Jung, J.; Aziz, N.; Kissil, J.L.; Pure, E. Targeting Fibroblast Activation Protein Inhibits Tumor Stromagenesis and Growth in Mice. J. Clin. Invest. 2009, 119, 3613–3625. [Google Scholar] [CrossRef] [PubMed]
- Calon, A.; Lonardo, E.; Berenguer-Llergo, A.; Espinet, E.; Hernando-Momblona, X.; Iglesias, M.; Sevillano, M.; Palomo-Ponce, S.; Tauriello, D.V.; Byrom, D.; et al. Stromal Gene Expression Defines Poor-Prognosis Subtypes in Colorectal Cancer. Nat. Genet. 2015, 47, 320–329. [Google Scholar] [CrossRef] [PubMed]
- Catenacci, D.V.; Junttila, M.R.; Karrison, T.; Bahary, N.; Horiba, M.N.; Nattam, S.R.; Marsh, R.; Wallace, J.; Kozloff, M.; Rajdev, L.; et al. Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients with Metastatic Pancreatic Cancer. J. Clin. Oncol. 2015, 33, 4284–4292. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.J.; Perera, R.M.; Wang, H.; Wu, D.C.; Liu, X.S.; Han, S.; Fitamant, J.; Jones, P.D.; Ghanta, K.S.; Kawano, S.; et al. Stromal Response to Hedgehog Signaling Restrains Pancreatic Cancer Progression. Proc. Natl. Acad. Sci. USA 2014, 111, E3091–E3100. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.; Lin, Y.; Shi, Y.; Li, B.; Liu, W.; Yin, W.; Dang, Y.; Chu, Y.; Fan, J.; He, R. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment Via STAT3-CCL2 Signaling. Cancer Res. 2016, 76, 4124–4135. [Google Scholar] [CrossRef]
- Feig, C.; Jones, J.O.; Kraman, M.; Wells, R.J.; Deonarine, A.; Chan, D.S.; Connell, C.M.; Roberts, E.W.; Zhao, Q.; Caballero, O.L.; et al. Targeting CXCL12 from Fap-Expressing Carcinoma-Associated Fibroblasts Synergizes with Anti-PD-L1 Immunotherapy in Pancreatic Cancer. Proc. Natl. Acad. Sci. USA 2013, 110, 20212–20217. [Google Scholar] [CrossRef]
- Jiang, L.; Li, X.; Zhang, Y.; Zhang, M.; Tang, Z.; Lv, K. Microarray and Bioinformatics Analyses of Gene Expression Profiles in Balb/C Murine Macrophage Polarization. Mol. Med. Rep. 2017, 16, 7382–7390. [Google Scholar] [CrossRef]
- Kumar, V.; Donthireddy, L.; Marvel, D.; Condamine, T.; Wang, F.; Lavilla-Alonso, S.; Hashimoto, A.; Vonteddu, P.; Behera, R.; Goins, M.A.; et al. Cancer-Associated Fibroblasts Neutralize the Anti-Tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors. Cancer Cell 2017, 32, 654–668. [Google Scholar] [CrossRef]
- De Monte, L.; Reni, M.; Tassi, E.; Clavenna, D.; Papa, I.; Recalde, H.; Braga, M.; Di Carlo, V.; Doglioni, C.; Protti, M.P. Intratumor T Helper Type 2 Cell Infiltrate Correlates with Cancer-Associated Fibroblast Thymic Stromal Lymphopoietin Production and Reduced Survival in Pancreatic Cancer. J. Exp. Med. 2011, 208, 469–478. [Google Scholar] [CrossRef]
- Tauriello, D.V.F.; Palomo-Ponce, S.; Stork, D.; Berenguer-Llergo, A.; Badia-Ramentol, J.; Iglesias, M.; Sevillano, M.; Ibiza, S.; Canellas, A.; Hernando-Momblona, X.; et al. TGF-beta Drives Immune Evasion in Genetically Reconstituted Colon Cancer Metastasis. Nature 2018, 554, 538–543. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Wang, R.; Xiong, S.; Wang, X.; Zhao, Z.; Bai, S.; Wang, Y.; Zhao, Y.; Cheng, B. Cancer-Associated Fibroblasts Promote the Stemness of CD24(+) Liver Cells via Paracrine Signaling. J. Mol. Med. (Berl) 2019, 97, 243–255. [Google Scholar] [CrossRef] [PubMed]
- Cannarile, M.A.; Weisser, M.; Jacob, W.; Jegg, A.M.; Ries, C.H.; Ruttinger, D. Colony-Stimulating Factor 1 Receptor (CSF1R) Inhibitors in Cancer Therapy. J. Immunother. Cancer 2017, 5, 53. [Google Scholar] [CrossRef] [PubMed]
- Beswick, E.J.; Grim, C.; Singh, A.; Aguirre, J.E.; Tafoya, M.; Qiu, S.; Rogler, G.; McKee, R.; Samedi, V.; Ma, T.Y.; et al. Expression of Programmed Death-Ligand 1 by Human Colonic CD90(+) Stromal Cells Differs between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells. Front. Immunol. 2018, 9. [Google Scholar] [CrossRef] [PubMed]
- Turley, S.J.; Cremasco, V.; Astarita, J.L. Immunological Hallmarks of Stromal Cells in the Tumour Microenvironment. Nat. Rev. Immunol. 2015, 15, 669–682. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Li, H.; Deng, Y.; Tai, Y.; Zeng, K.; Zhang, Y.; Liu, W.; Zhang, Q.; Yang, Y. Cancer-Associated Fibroblasts Induce Pdl1+ Neutrophils through the IL6-STAT3 Pathway That Foster Immune Suppression in Hepatocellular Carcinoma. Cell Death Dis. 2018, 9, 422. [Google Scholar] [CrossRef] [PubMed]
- Menard, C.; Blay, J.Y.; Borg, C.; Michiels, S.; Ghiringhelli, F.; Robert, C.; Nonn, C.; Chaput, N.; Taieb, J.; Delahaye, N.F.; et al. Natural Killer Cell IFN-Gamma Levels Predict Long-Term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor-Bearing Patients. Cancer Res. 2009, 69, 3563–3569. [Google Scholar] [CrossRef] [PubMed]
- Angka, L.; Martel, A.B.; Kilgour, M.; Jeong, A.; Sadiq, M.; de Souza, C.T.; Baker, L.; Kennedy, M.A.; Kekre, N.; Auer, R.C. Natural Killer Cell IFN-gamma Secretion Is Profoundly Suppressed Following Colorectal Cancer Surgery. Ann. Surg. Oncol. 2018, 25, 3747–3754. [Google Scholar] [CrossRef]
- Cooper, M.A.; Fehniger, T.A.; Turner, S.C.; Chen, K.S.; Ghaheri, B.A.; Ghayur, T.; Carson, W.E.; Caligiuri, M.A. Human Natural Killer Cells: A Unique Innate Immunoregulatory Role for the CD56(Bright) Subset. Blood 2001, 97, 3146–3151. [Google Scholar] [CrossRef]
- Wang, W.; Erbe, A.K.; Hank, J.A.; Morris, Z.S.; Sondel, P.M. NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy. Front. Immunol. 2015, 6, 368. [Google Scholar] [CrossRef]
- Easom, N.J.W.; Stegmann, K.A.; Swadling, L.; Pallett, L.J.; Burton, A.R.; Odera, D.; Schmidt, N.; Huang, W.C.; Fusai, G.; Davidson, B.; et al. IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction. Front. Immunol. 2018, 9, 1009. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, C.; Xu, J.; Huang, Q.; Huang, M.; Wen, H.; Zhang, C.; Wang, J.; Song, J.; Zheng, M.; Sun, H.; et al. High NKG2A Expression Contributes to NK Cell Exhaustion and Predicts a Poor Prognosis of Patients with Liver Cancer. Oncoimmunology 2017, 6, e1264562. [Google Scholar] [CrossRef] [PubMed]
- Cai, L.; Zhang, Z.; Zhou, L.; Wang, H.; Fu, J.; Zhang, S.; Shi, M.; Zhang, H.; Yang, Y.; Wu, H.; et al. Functional Impairment in Circulating and Intrahepatic NK Cells and Relative Mechanism in Hepatocellular Carcinoma Patients. Clin. Immunol. 2008, 129, 428–437. [Google Scholar] [CrossRef] [PubMed]
- Sui, Q.; Zhang, J.; Sun, X.; Zhang, C.; Han, Q.; Tian, Z. Nk Cells Are the Crucial Antitumor Mediators When STAT3-Mediated Immunosuppression Is Blocked in Hepatocellular Carcinoma. J. Immunol. 2014, 193, 2016–2023. [Google Scholar] [CrossRef] [PubMed]
- Bang, S.; Kim, H.S.; Choo, Y.S.; Park, S.W.; Chung, J.B.; Song, S.Y. Differences in Immune Cells Engaged in Cell-Mediated Immunity after Chemotherapy for Far Advanced Pancreatic Cancer. Pancreas 2006, 32, 29–36. [Google Scholar] [CrossRef]
- Jobin, G.; Rodriguez-Suarez, R.; Betito, K. Association between Natural Killer Cell Activity and Colorectal Cancer in High-Risk Subjects Undergoing Colonoscopy. Gastroenterology 2017, 153, 980–987. [Google Scholar] [CrossRef] [PubMed]
- Wirsdorfer, F.; Bangen, J.M.; Pastille, E.; Hansen, W.; Flohe, S.B. Breaking the Co-Operation between Bystander T-Cells and Natural Killer Cells Prevents the Development of Immunosuppression after Traumatic Skeletal Muscle Injury in Mice. Clin. Sci. (Lond.) 2015, 128, 825–838. [Google Scholar] [CrossRef]
- Duan, X.; Deng, L.; Chen, X.; Lu, Y.; Zhang, Q.; Zhang, K.; Hu, Y.; Zeng, J.; Sun, W. Clinical Significance of the Immunostimulatory MHC Class I Chain-Related Molecule a and NKG2D Receptor on NK Cells in Pancreatic Cancer. Med. Oncol. 2011, 28, 466–474. [Google Scholar] [CrossRef]
- Jun, E.; Song, A.Y.; Choi, J.W.; Lee, H.H.; Kim, M.Y.; Ko, D.H.; Kang, H.J.; Kim, S.W.; Bryceson, Y.; Kim, S.C.; et al. Progressive Impairment of Nk Cell Cytotoxic Degranulation Is Associated with TGF-Beta1 Deregulation and Disease Progression in Pancreatic Cancer. Front. Immunol. 2019, 10, 1354. [Google Scholar] [CrossRef]
- Wang, S.; Hong, S.; Wezeman, M.; Qian, J.; Yang, J.; Yi, Q. Dendritic Cell Vaccine but Not Idiotype-KLH Protein Vaccine Primes Therapeutic Tumor-Specific Immunity against Multiple Myeloma. Front. Biosci. 2007, 12, 3566–3575. [Google Scholar] [CrossRef]
- Liu, N.; Jiang, Y.; Chen, J.; Nan, H.; Zhao, Y.; Chu, X.; Wang, A.; Wang, D.; Qin, T.; Gao, S.; et al. IL-33 Drives the Antitumor Effects of Dendritic Cells Via the Induction of Tc9 Cells. Cell Mol. Immunol. 2019, 16, 644–651. [Google Scholar] [CrossRef] [PubMed]
- Ouyang, F.Z.; Wu, R.Q.; Wei, Y.; Liu, R.X.; Yang, D.; Xiao, X.; Zheng, L.; Li, B.; Lao, X.M.; Kuang, D.M. Dendritic Cell-Elicited B-Cell Activation Fosters Immune Privilege via IL-10 Signals in Hepatocellular Carcinoma. Nat. Commun. 2016, 7, 13453. [Google Scholar] [CrossRef] [PubMed]
- Yuan, A.; Steigen, S.E.; Goll, R.; Vonen, B.; Husbekk, A.; Cui, G.; Florholmen, J. Dendritic Cell Infiltration Pattern Along the Colorectal Adenoma-Carcinoma Sequence. APMIS 2008, 116, 445–456. [Google Scholar] [CrossRef]
- Pryczynicz, A.; Cepowicz, D.; Zareba, K.; Gryko, M.; Holody-Zareba, J.; Kedra, B.; Kemona, A.; Guzinska-Ustymowicz, K. Dysfunctions in the Mature Dendritic Cells Are Associated with the Presence of Metastases of Colorectal Cancer in the Surrounding Lymph Nodes. Gastroenterol Res. Pract. 2016, 2016, 2405437. [Google Scholar] [CrossRef] [PubMed]
- Sung, G.H.; Chang, H.; Lee, J.Y.; Song, S.Y.; Kim, H.S. Pancreatic-Cancer-Cell-Derived Trefoil Factor 2 Impairs Maturation and Migration of Human Monocyte-Derived Dendritic Cells in Vitro. Anim. Cells Syst. (Seoul) 2018, 22, 368–381. [Google Scholar] [CrossRef] [PubMed]
- Barilla, R.M.; Diskin, B.; Caso, R.C.; Lee, K.B.; Mohan, N.; Buttar, C.; Adam, S.; Sekendiz, Z.; Wang, J.; Salas, R.D.; et al. Specialized Dendritic Cells Induce Tumor-Promoting IL-10(+)IL-17(+) Foxp3(Neg) Regulatory CD4(+) T Cells in Pancreatic Carcinoma. Nat. Commun. 2019, 10, 1424. [Google Scholar] [CrossRef] [PubMed]
- Chihara, N.; Madi, A.; Karwacz, K.; Awasthi, A.; Kuchroo, V.K. Differentiation and Characterization of Tr1 Cells. Curr. Protoc. Immunol. 2016, 113, 3–27. [Google Scholar]
- Yao, Y.; Vent-Schmidt, J.; McGeough, M.D.; Wong, M.; Hoffman, H.M.; Steiner, T.S.; Levings, M.K. Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism. J. Immunol. 2015, 195, 488–497. [Google Scholar] [CrossRef]
- Hu, Z.; Ma, Y.; Shang, Z.; Hu, S.; Liang, K.; Liang, W.; Xing, X.; Wang, Y.; Du, X. Improving Immunotherapy for Colorectal Cancer Using Dendritic Cells Combined with Anti-Programmed Death-Ligand in Vitro. Oncol. Lett. 2018, 15, 5345–5351. [Google Scholar] [CrossRef]
- Yang, L.; Zhang, Y. Tumor-Associated Macrophages, Potential Targets for Cancer Treatment. Biomark Res. 2017, 5, 25. [Google Scholar] [CrossRef]
- Mantovani, A.; Sica, A. Macrophages, Innate Immunity and Cancer: Balance, Tolerance, and Diversity. Curr. Opin. Immunol. 2010, 22, 231–237. [Google Scholar] [CrossRef] [PubMed]
- Fu, X.T.; Song, K.; Zhou, J.; Shi, Y.H.; Liu, W.R.; Shi, G.M.; Gao, Q.; Wang, X.Y.; Ding, Z.B.; Fan, J. Tumor-Associated Macrophages Modulate Resistance to Oxaliplatin Via Inducing Autophagy in Hepatocellular Carcinoma. Cancer Cell Int. 2019, 19, 71. [Google Scholar] [CrossRef] [PubMed]
- Waniczek, D.; Lorenc, Z.; Snietura, M.; Wesecki, M.; Kopec, A.; Muc-Wierzgon, M. Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer. Arch. Immunol. Ther. Exp. (Warsz) 2017, 65, 445–454. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cui, Y.L.; Li, H.K.; Zhou, H.Y.; Zhang, T.; Li, Q. Correlations of Tumor-Associated Macrophage Subtypes with Liver Metastases of Colorectal Cancer. Asian Pac. J. Cancer Prev. 2013, 14, 1003–1007. [Google Scholar] [CrossRef] [PubMed]
- Yoshikawa, K.; Mitsunaga, S.; Kinoshita, T.; Konishi, M.; Takahashi, S.; Gotohda, N.; Kato, Y.; Aizawa, M.; Ochiai, A. Impact of Tumor-Associated Macrophages on Invasive Ductal Carcinoma of the Pancreas Head. Cancer Sci. 2012, 103, 2012–2020. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.B.; Jia, Q.A.; Wang, H.; Hu, C.X.; Sun, D.; Jiang, R.D.; Zhang, Z.L. High-Mobility Group Protein Box1 Expression Correlates with Peritumoral Macrophage Infiltration and Unfavorable Prognosis in Patients with Hepatocellular Carcinoma and Cirrhosis. BMC Cancer 2016, 16, 880. [Google Scholar] [CrossRef] [PubMed]
- Movahedi, K.; Van Ginderachter, J.A. The Ontogeny and Microenvironmental Regulation of Tumor-Associated Macrophages. Antioxid. Redox Signal. 2016, 25, 775–791. [Google Scholar] [CrossRef]
- Sanford, D.E.; Belt, B.A.; Panni, R.Z.; Mayer, A.; Deshpande, A.D.; Carpenter, D.; Mitchem, J.B.; Plambeck-Suess, S.M.; Worley, L.A.; Goetz, B.D.; et al. Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis. Clin. Cancer Res. 2013, 19, 3404–3415. [Google Scholar] [CrossRef] [Green Version]
- Bartneck, M.; Schrammen, P.L.; Mockel, D.; Govaere, O.; Liepelt, A.; Krenkel, O.; Ergen, C.; McCain, M.V.; Eulberg, D.; Luedde, T.; et al. The CCR2(+) Macrophage Subset Promotes Pathogenic Angiogenesis for Tumor Vascularization in Fibrotic Livers. Cell Mol. Gastroenterol Hepatol. 2019, 7, 371–390. [Google Scholar] [CrossRef]
- Wei, S.; Nandi, S.; Chitu, V.; Yeung, Y.G.; Yu, W.; Huang, M.; Williams, L.T.; Lin, H.; Stanley, E.R. Functional Overlap but Differential Expression of CSF-1 and IL-34 in Their CSF-1 Receptor-Mediated Regulation of Myeloid Cells. J. Leukoc. Biol. 2010, 88, 495–505. [Google Scholar] [CrossRef]
- Wang, Y.; Colonna, M. Interkeukin-34, a Cytokine Crucial for the Differentiation and Maintenance of Tissue Resident Macrophages and Langerhans Cells. Eur. J. Immunol. 2014, 44, 1575–1581. [Google Scholar] [CrossRef] [PubMed]
- Habtezion, A.; Edderkaoui, M.; Pandol, S.J. Macrophages and Pancreatic Ductal Adenocarcinoma. Cancer Lett. 2016, 381, 211–216. [Google Scholar] [CrossRef] [PubMed]
- Huang, C.; Li, Z.; Li, N.; Li, Y.; Chang, A.; Zhao, T.; Wang, X.; Wang, H.; Gao, S.; Yang, S.; et al. Interleukin 35 Expression Correlates with Microvessel Density in Pancreatic Ductal Adenocarcinoma, Recruits Monocytes, and Promotes Growth and Angiogenesis of Xenograft Tumors in Mice. Gastroenterology 2018, 154, 675–688. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Knolhoff, B.L.; Meyer, M.A.; Nywening, T.M.; West, B.L.; Luo, J.; Wang-Gillam, A.; Goedegebuure, S.P.; Linehan, D.C.; DeNardo, D.G. CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T-Cell Checkpoint Immunotherapy in Pancreatic Cancer Models. Cancer Res. 2014, 74, 5057–5069. [Google Scholar] [CrossRef] [PubMed]
- Petty, A.J.; Yang, Y. Tumor-Associated Macrophages: Implications in Cancer Immunotherapy. Immunotherapy 2017, 9, 289–302. [Google Scholar] [CrossRef] [PubMed]
- Beatty, G.L.; Winograd, R.; Evans, R.A.; Long, K.B.; Luque, S.L.; Lee, J.W.; Clendenin, C.; Gladney, W.L.; Knoblock, D.M.; Guirnalda, P.D.; et al. Exclusion of T Cells from Pancreatic Carcinomas in Mice Is Regulated by Ly6c(Low) F4/80(+) Extratumoral Macrophages. Gastroenterology 2015, 149, 201–210. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Li, J.; Salcedo, R.; Mivechi, N.F.; Trinchieri, G.; Horuzsko, A. The Proinflammatory Myeloid Cell Receptor Trem-1 Controls Kupffer Cell Activation and Development of Hepatocellular Carcinoma. Cancer Res 2012, 72, 3977–3986. [Google Scholar] [CrossRef] [PubMed]
- Greten, F.R.; Arkan, M.C.; Bollrath, J.; Hsu, L.C.; Goode, J.; Miething, C.; Goktuna, S.I.; Neuenhahn, M.; Fierer, J.; Paxian, S.; et al. NF-Kappa-b Is a Negative Regulator of IL-1beta Secretion as Revealed by Genetic and Pharmacological Inhibition of Ikkbeta. Cell 2007, 130, 918–931. [Google Scholar] [CrossRef] [PubMed]
- Zhong, X.; Chen, B.; Yang, Z. The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression. Cell Physiol. Biochem. 2018, 45, 356–365. [Google Scholar] [CrossRef]
- Khorana, A.A.; Ryan, C.K.; Cox, C.; Eberly, S.; Sahasrabudhe, D.M. Vascular Endothelial Growth Factor, CD68, and Epidermal Growth Factor Receptor Expression and Survival in Patients with Stage II and Stage III Colon Carcinoma: A Role for the Host Response in Prognosis. Cancer 2003, 97, 960–968. [Google Scholar] [CrossRef]
- Esposito, I.; Menicagli, M.; Funel, N.; Bergmann, F.; Boggi, U.; Mosca, F.; Bevilacqua, G.; Campani, D. Inflammatory Cells Contribute to the Generation of an Angiogenic Phenotype in Pancreatic Ductal Adenocarcinoma. J. Clin. Pathol. 2004, 57, 630–636. [Google Scholar] [CrossRef] [PubMed]
- Dalton, H.J.; Pradeep, S.; McGuire, M.; Hailemichael, Y.; Ma, S.; Lyons, Y.; Armaiz-Pena, G.N.; Previs, R.A.; Hansen, J.M.; Rupaimoole, R.; et al. Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFExpression. Clin. Cancer Res. 2017, 23, 7034–7046. [Google Scholar] [CrossRef] [PubMed]
- Bayne, L.J.; Beatty, G.L.; Jhala, N.; Clark, C.E.; Rhim, A.D.; Stanger, B.Z.; Vonderheide, R.H. Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer. Cancer Cell 2012, 21, 822–835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qu, P.; Wang, L.Z.; Lin, P.C. Expansion and Functions of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Cancer Lett. 2016, 380, 253–256. [Google Scholar] [CrossRef] [PubMed]
- Kamran, N.; Li, Y.; Sierra, M.; Alghamri, M.S.; Kadiyala, P.; Appelman, H.D.; Edwards, M.; Lowenstein, P.R.; Castro, M.G. Melanoma Induced Immunosuppression Is Mediated by Hematopoietic Dysregulation. Oncoimmunology 2018, 7, e1408750. [Google Scholar] [CrossRef] [PubMed]
- Chang, J.H.; Jiang, Y.; Pillarisetty, V.G. Role of Immune Cells in Pancreatic Cancer from Bench to Clinical Application: An Updated Review. Medicine (Baltimore) 2016, 95, e5541. [Google Scholar] [CrossRef]
- Felix, K.; Gaida, M.M. Neutrophil-Derived Proteases in the Microenvironment of Pancreatic Cancer -Active Players in Tumor Progression. Int. J. Biol. Sci. 2016, 12, 302–313. [Google Scholar] [CrossRef] [Green Version]
- Movahedi, K.; Guilliams, M.; Van den Bossche, J.; Van den Bergh, R.; Gysemans, C.; Beschin, A.; De Baetselier, P.; Van Ginderachter, J.A. Identification of Discrete Tumor-Induced Myeloid-Derived Suppressor Cell Subpopulations with Distinct T Cell-Suppressive Activity. Blood 2008, 111, 4233–4244. [Google Scholar] [CrossRef]
- Bronte, V.; Brandau, S.; Chen, S.H.; Colombo, M.P.; Frey, A.B.; Greten, T.F.; Mandruzzato, S.; Murray, P.J.; Ochoa, A.; Ostrand-Rosenberg, S.; et al. Recommendations for Myeloid-Derived Suppressor Cell Nomenclature and Characterization Standards. Nat. Commun. 2016, 7, 12150. [Google Scholar] [CrossRef]
- Karakasheva, T.A.; Dominguez, G.A.; Hashimoto, A.; Lin, E.W.; Chiu, C.; Sasser, K.; Lee, J.W.; Beatty, G.L.; Gabrilovich, D.I.; Rustgi, A.K. CD38+ M-MDSC Expansion Characterizes a Subset of Advanced Colorectal Cancer Patients. JCI Insight 2018, 3. [Google Scholar] [CrossRef]
- Porembka, M.R.; Mitchem, J.B.; Belt, B.A.; Hsieh, C.S.; Lee, H.M.; Herndon, J.; Gillanders, W.E.; Linehan, D.C.; Goedegebuure, P. Pancreatic Adenocarcinoma Induces Bone Marrow Mobilization of Myeloid-Derived Suppressor Cells Which Promote Primary Tumor Growth. Cancer Immunol. Immunother. 2012, 61, 1373–1385. [Google Scholar] [CrossRef] [PubMed]
- Kapanadze, T.; Gamrekelashvili, J.; Ma, C.; Chan, C.; Zhao, F.; Hewitt, S.; Zender, L.; Kapoor, V.; Felsher, D.W.; Manns, M.P.; et al. Regulation of Accumulation and Function of Myeloid Derived Suppressor Cells in Different Murine Models of Hepatocellular Carcinoma. J. Hepatol. 2013, 59, 1007–1013. [Google Scholar] [CrossRef] [PubMed]
- Hoechst, B.; Ormandy, L.A.; Ballmaier, M.; Lehner, F.; Kruger, C.; Manns, M.P.; Greten, T.F.; Korangy, F. A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4(+)CD25(+)Foxp3(+) T Cells. Gastroenterology 2008, 135, 234–243. [Google Scholar] [CrossRef] [PubMed]
- Hoechst, B.; Voigtlaender, T.; Ormandy, L.; Gamrekelashvili, J.; Zhao, F.; Wedemeyer, H.; Lehner, F.; Manns, M.P.; Greten, T.F.; Korangy, F. Myeloid Derived Suppressor Cells Inhibit Natural Killer Cells in Patients with Hepatocellular Carcinoma Via the Nkp30 Receptor. Hepatology 2009, 50, 799–807. [Google Scholar] [CrossRef] [PubMed]
- Ibrahim, M.L.; Klement, J.D.; Lu, C.; Redd, P.S.; Xiao, W.; Yang, D.; Browning, D.D.; Savage, N.M.; Buckhaults, P.J.; Morse, H.C., 3rd; et al. Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis. Cell Rep. 2018, 25, 3036–3046. [Google Scholar] [CrossRef] [PubMed]
- Guidotti, L.G.; Inverso, D.; Sironi, L.; Di Lucia, P.; Fioravanti, J.; Ganzer, L.; Fiocchi, A.; Vacca, M.; Aiolfi, R.; Sammicheli, S.; et al. Immunosurveillance of the Liver by Intravascular Effector CD8(+) T Cells. Cell 2015, 161, 486–500. [Google Scholar] [CrossRef] [PubMed]
- Garrido, F.; Cabrera, T.; Aptsiauri, N. “Hard” and “Soft” Lesions Underlying the HLA Class I Alterations in Cancer Cells: Implications for Immunotherapy. Int. J. Cancer 2010, 127, 249–256. [Google Scholar] [CrossRef]
- Fridman, W.H.; Pages, F.; Sautes-Fridman, C.; Galon, J. The Immune Contexture in Human Tumours: Impact on Clinical Outcome. Nat. Rev. Cancer 2012, 12, 298–306. [Google Scholar] [CrossRef]
- Miksch, R.C.; Schoenberg, M.B.; Weniger, M.; Bosch, F.; Ormanns, S.; Mayer, B.; Werner, J.; Bazhin, A.V.; D’Haese, J.G. Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer. Cancers (Basel) 2019, 11, 39. [Google Scholar] [CrossRef]
- Hagland, H.R.; Lea, D.; Watson, M.M.; Soreide, K. Correlation of Blood T-Cells to Intratumoural Density and Location of CD3(+) and CD8(+) T-Cells in Colorectal Cancer. Anticancer. Res. 2017, 37, 675–683. [Google Scholar] [CrossRef]
- Xu, X.; Tan, Y.; Qian, Y.; Xue, W.; Wang, Y.; Du, J.; Jin, L.; Ding, W. Clinicopathologic and Prognostic Significance of Tumor-Infiltrating CD8+ T Cells in Patients with Hepatocellular Carcinoma: A Meta-Analysis. Medicine (Baltimore) 2019, 98, e13923. [Google Scholar] [CrossRef] [PubMed]
- Ino, Y.; Yamazaki-Itoh, R.; Shimada, K.; Iwasaki, M.; Kosuge, T.; Kanai, Y.; Hiraoka, N. Immune Cell Infiltration as an Indicator of the Immune Microenvironment of Pancreatic Cancer. Br. J. Cancer 2013, 108, 914–923. [Google Scholar] [CrossRef] [PubMed]
- Peranzoni, E.; Lemoine, J.; Vimeux, L.; Feuillet, V.; Barrin, S.; Kantari-Mimoun, C.; Bercovici, N.; Guerin, M.; Biton, J.; Ouakrim, H.; et al. Macrophages Impede CD8 T Cells from Reaching Tumor Cells and Limit the Efficacy of Anti-PD-1 Treatment. Proc. Natl. Acad. Sci. USA 2018, 115, E4041–E4050. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S.; Zhong, M.; Wang, C.; Xu, Y.; Gao, W.Q.; Zhang, Y. CCL5-Deficiency Enhances Intratumoral Infiltration of CD8(+) T Cells in Colorectal Cancer. Cell Death Dis. 2018, 9, 766. [Google Scholar] [CrossRef] [PubMed]
- Katlinski, K.V.; Gui, J.; Katlinskaya, Y.V.; Ortiz, A.; Chakraborty, R.; Bhattacharya, S.; Carbone, C.J.; Beiting, D.P.; Girondo, M.A.; Peck, A.R.; et al. Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment. Cancer Cell 2017, 31, 194–207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schumacher, T.N.; Schreiber, R.D. Neoantigens in Cancer Immunotherapy. Science 2015, 348, 69–74. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Cardell, S.L. The Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity-Suppression of Tumor Immunity in the Intestine. Front. Immunol. 2017, 8, 1945. [Google Scholar] [CrossRef]
- Endig, J.; Buitrago-Molina, L.E.; Marhenke, S.; Reisinger, F.; Saborowski, A.; Schutt, J.; Limbourg, F.; Konecke, C.; Schreder, A.; Michael, A.; et al. Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development. Cancer Cell 2016, 30, 308–323. [Google Scholar] [CrossRef] [Green Version]
- Chiang, E.Y.; Kolumam, G.A.; Yu, X.; Francesco, M.; Ivelja, S.; Peng, I.; Gribling, P.; Shu, J.; Lee, W.P.; Refino, C.J.; et al. Targeted Depletion of Lymphotoxin-Alpha-Expressing Th1 and Th17 Cells Inhibits Autoimmune Disease. Nat. Med. 2009, 15, 766–773. [Google Scholar] [CrossRef]
- Finkin, S.; Yuan, D.; Stein, I.; Taniguchi, K.; Weber, A.; Unger, K.; Browning, J.L.; Goossens, N.; Nakagawa, S.; Gunasekaran, G.; et al. Ectopic Lymphoid Structures Function as Microniches for Tumor Progenitor Cells in Hepatocellular Carcinoma. Nat. Immunol. 2015, 16, 1235–1244. [Google Scholar] [CrossRef]
- Sautes-Fridman, C.; Lawand, M.; Giraldo, N.A.; Kaplon, H.; Germain, C.; Fridman, W.H.; Dieu-Nosjean, M.C. Tertiary Lymphoid Structures in Cancers: Prognostic Value, Regulation, and Manipulation for Therapeutic Intervention. Front. Immunol. 2016, 7, 407. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Protti, M.P.; De Monte, L. Cross-Talk within the Tumor Microenvironment Mediates Th2-Type Inflammation in Pancreatic Cancer. Oncoimmunology 2012, 1, 89–91. [Google Scholar] [CrossRef] [PubMed]
- Ling, A.; Lundberg, I.V.; Eklof, V.; Wikberg, M.L.; Oberg, A.; Edin, S.; Palmqvist, R. The Infiltration, and Prognostic Importance, of Th1 Lymphocytes Vary in Molecular Subgroups of Colorectal Cancer. J. Pathol. Clin. Res. 2016, 2, 21–31. [Google Scholar] [CrossRef] [PubMed]
- Liu, V.C.; Wong, L.Y.; Jang, T.; Shah, A.H.; Park, I.; Yang, X.; Zhang, Q.; Lonning, S.; Teicher, B.A.; Lee, C. Tumor Evasion of the Immune System by Converting CD4+CD25- T Cells into CD4+CD25+ T Regulatory Cells: Role of Tumor-Derived TGF-Beta. J. Immunol. 2007, 178, 2883–2892. [Google Scholar] [CrossRef] [PubMed]
- Hindley, J.P.; Ferreira, C.; Jones, E.; Lauder, S.N.; Ladell, K.; Wynn, K.K.; Betts, G.J.; Singh, Y.; Price, D.A.; Godkin, A.J.; et al. Analysis of the T-Cell Receptor Repertoires of Tumor-Infiltrating Conventional and Regulatory T Cells Reveals No Evidence for Conversion in Carcinogen-Induced Tumors. Cancer Res. 2011, 71, 736–746. [Google Scholar] [CrossRef]
- Jarnicki, A.G.; Lysaght, J.; Todryk, S.; Mills, K.H. Suppression of Antitumor Immunity by IL-10 and TGF-Beta-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and Cd8+ Regulatory T Cells. J. Immunol. 2006, 177, 896–904. [Google Scholar] [CrossRef]
- Correale, P.; Rotundo, M.S.; Del Vecchio, M.T.; Remondo, C.; Migali, C.; Ginanneschi, C.; Tsang, K.Y.; Licchetta, A.; Mannucci, S.; Loiacono, L.; et al. Regulatory (Foxp3+) T-Cell Tumor Infiltration Is a Favorable Prognostic Factor in Advanced Colon Cancer Patients Undergoing Chemo or Chemoimmunotherapy. J. Immunother. 2010, 33, 435–441. [Google Scholar] [CrossRef]
- Gao, Q.; Qiu, S.J.; Fan, J.; Zhou, J.; Wang, X.Y.; Xiao, Y.S.; Xu, Y.; Li, Y.W.; Tang, Z.Y. Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated with Prognosis of Hepatocellular Carcinoma after Resection. J. Clin. Oncol. 2007, 25, 2586–2593. [Google Scholar] [CrossRef]
- Zhang, Y.; Zoltan, M.; Riquelme, E.; Xu, H.; Sahin, I.; Castro-Pando, S.; Montiel, M.F.; Chang, K.; Jiang, Z.; Ling, J.; et al. Immune Cell Production of Interleukin 17 Induces Stem Cell Features of Pancreatic Intraepithelial Neoplasia Cells. Gastroenterology 2018, 155, 210–223. [Google Scholar] [CrossRef]
- Razi, S.; Baradaran Noveiry, B.; Keshavarz-Fathi, M.; Rezaei, N. IL-17 and Colorectal Cancer: From Carcinogenesis to Treatment. Cytokine 2019, 116, 7–12. [Google Scholar] [CrossRef]
- Gomes, A.L.; Teijeiro, A.; Buren, S.; Tummala, K.S.; Yilmaz, M.; Waisman, A.; Theurillat, J.P.; Perna, C.; Djouder, N. Metabolic Inflammation-Associated IL-17a Causes Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma. Cancer Cell 2016, 30, 161–175. [Google Scholar] [CrossRef] [PubMed]
- Amicarella, F.; Muraro, M.G.; Hirt, C.; Cremonesi, E.; Padovan, E.; Mele, V.; Governa, V.; Han, J.; Huber, X.; Droeser, R.A.; et al. Dual Role of Tumour-Infiltrating T Helper 17 Cells in Human Colorectal Cancer. Gut 2017, 66, 692–704. [Google Scholar] [CrossRef] [PubMed]
- Lu, P.H.; Negrin, R.S. A Novel Population of Expanded Human CD3+CD56+ Cells Derived from T Cells with Potent in Vivo Antitumor Activity in Mice with Severe Combined Immunodeficiency. J. Immunol. 1994, 153, 1687–1696. [Google Scholar] [PubMed]
- Introna, M.; Franceschetti, M.; Ciocca, A.; Borleri, G.; Conti, E.; Golay, J.; Rambaldi, A. Rapid and Massive Expansion of Cord Blood-Derived Cytokine-Induced Killer Cells: An Innovative Proposal for the Treatment of Leukemia Relapse after Cord Blood Transplantation. Bone Marrow Transplant. 2006, 38, 621–627. [Google Scholar] [CrossRef] [PubMed]
- Linn, Y.C.; Lau, L.C.; Hui, K.M. Generation of Cytokine-Induced Killer Cells from Leukaemic Samples with in Vitro Cytotoxicity against Autologous and Allogeneic Leukaemic Blasts. Br. J. Haematol. 2002, 116, 78–86. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.K.; Kim, Y.G.; Kim, J.S.; Park, E.J.; Kim, B.; Park, K.H.; Kang, J.S.; Hong, J.T.; Kim, Y.; Han, S.B. Cytokine-Induced Killer Cells Interact with Tumor Lysate-Pulsed Dendritic Cells via CCR5 Signaling. Cancer Lett. 2016, 378, 142–149. [Google Scholar] [CrossRef] [PubMed]
- Verneris, M.R.; Karimi, M.; Baker, J.; Jayaswal, A.; Negrin, R.S. Role of NKG2D Signaling in the Cytotoxicity of Activated and Expanded CD8+ T Cells. Blood 2004, 103, 3065–3072. [Google Scholar] [CrossRef]
- Schmidt, T.L.; Negrin, R.S.; Contag, C.H. A Killer Choice for Cancer Immunotherapy. Immunol. Res. 2014, 58, 300–306. [Google Scholar] [CrossRef]
- Hoffman, W.; Lakkis, F.G.; Chalasani, G. B Cells, Antibodies, and More. Clin. J. Am. Soc. Nephrol. 2016, 11, 137–154. [Google Scholar] [CrossRef]
- Lund, F.E.; Hollifield, M.; Schuer, K.; Lines, J.L.; Randall, T.D.; Garvy, B.A. B Cells Are Required for Generation of Protective Effector and Memory CD4 Cells in Response to Pneumocystis Lung Infection. J. Immunol. 2006, 176, 6147–6154. [Google Scholar] [CrossRef]
- O’Neill, S.K.; Cao, Y.; Hamel, K.M.; Doodes, P.D.; Hutas, G.; Finnegan, A. Expression of CD80/86 on B Cells is Essential for Autoreactive T Cell Activation and the Development of Arthritis. J. Immunol. 2007, 179, 5109–5116. [Google Scholar] [CrossRef] [PubMed]
- Barr, T.A.; Brown, S.; Mastroeni, P.; Gray, D. TLR and B Cell Receptor Signals to B Cells Differentially Program Primary and Memory Th1 Responses to Salmonella Enterica. J. Immunol. 2010, 185, 2783–2789. [Google Scholar] [CrossRef] [PubMed]
- Shah, S.; Divekar, A.A.; Hilchey, S.P.; Cho, H.M.; Newman, C.L.; Shin, S.U.; Nechustan, H.; Challita-Eid, P.M.; Segal, B.M.; Yi, K.H.; et al. Increased Rejection of Primary Tumors in Mice Lacking B Cells: Inhibition of Anti-Tumor CTL and Th1 Cytokine Responses by B Cells. Int. J. Cancer 2005, 117, 574–586. [Google Scholar] [CrossRef] [PubMed]
- Thorn, M.; Point, G.R.; Burga, R.A.; Nguyen, C.T.; Joseph Espat, N.; Katz, S.C. Liver Metastases Induce Reversible Hepatic B Cell Dysfunction Mediated by Gr-1+CD11b+ Myeloid Cells. J. Leukoc. Biol. 2014, 96, 883–894. [Google Scholar] [CrossRef] [PubMed]
- Xue, H.; Lin, F.; Tan, H.; Zhu, Z.Q.; Zhang, Z.Y.; Zhao, L. Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in Hbv-Induced Hepatocellular Carcinoma. PLoS ONE 2016, 11, e0154815. [Google Scholar] [CrossRef] [PubMed]
- Wejksza, K.; Lee-Chang, C.; Bodogai, M.; Bonzo, J.; Gonzalez, F.J.; Lehrmann, E.; Becker, K.; Biragyn, A. Cancer-Produced Metabolites of 5-Lipoxygenase Induce Tumor-Evoked Regulatory B Cells Via Peroxisome Proliferator-Activated Receptor Alpha. J. Immunol. 2013, 190, 2575–2584. [Google Scholar] [CrossRef] [PubMed]
- Khlaiphuengsin, A.; Chuaypen, N.; Pinjaroen, N.; Sirichindakul, B.; Hirankarn, N.; Tangkijvanich, P. Plasma B-Cell Activating Factor Levels and Polymorphisms in Hepatitis B-Related Hepatocellular Carcinoma: Clinical Correlation and Prognosis. Asian Pac. J. Allergy Immunol. 2019. [Google Scholar]
- Pylayeva-Gupta, Y.; Das, S.; Handler, J.S.; Hajdu, C.H.; Coffre, M.; Koralov, S.B.; Bar-Sagi, D. IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia. Cancer Discov. 2016, 6, 247–255. [Google Scholar] [CrossRef]
- Gunderson, A.J.; Kaneda, M.M.; Tsujikawa, T.; Nguyen, A.V.; Affara, N.I.; Ruffell, B.; Gorjestani, S.; Liudahl, S.M.; Truitt, M.; Olson, P.; et al. Bruton Tyrosine Kinase-Dependent Immune Cell Cross-Talk Drives Pancreas Cancer. Cancer Discov. 2016, 6, 270–285. [Google Scholar] [CrossRef]
- Garnelo, M.; Tan, A.; Her, Z.; Yeong, J.; Lim, C.J.; Chen, J.; Lim, K.H.; Weber, A.; Chow, P.; Chung, A.; et al. Interaction between Tumour-Infiltrating B Cells and T Cells Controls the Progression of Hepatocellular Carcinoma. Gut 2017, 66, 342–351. [Google Scholar] [CrossRef]
- Schneider, C.; Teufel, A.; Yevsa, T.; Staib, F.; Hohmeyer, A.; Walenda, G.; Zimmermann, H.W.; Vucur, M.; Huss, S.; Gassler, N.; et al. Adaptive Immunity Suppresses Formation and Progression of Diethylnitrosamine-Induced Liver Cancer. Gut 2012, 61, 1733–1743. [Google Scholar] [CrossRef] [PubMed]
- Berntsson, J.; Nodin, B.; Eberhard, J.; Micke, P.; Jirstrom, K. Prognostic Impact of Tumour-Infiltrating B Cells and Plasma Cells in Colorectal Cancer. Int. J. Cancer 2016, 139, 1129–1139. [Google Scholar] [CrossRef] [PubMed]
- Bassiri, H.; Das, R.; Nichols, K.E. Invariant Nkt Cells: Killers and Conspirators against Cancer. Oncoimmunology 2013, 2, e27440. [Google Scholar] [CrossRef] [PubMed]
- Bricard, G.; Cesson, V.; Devevre, E.; Bouzourene, H.; Barbey, C.; Rufer, N.; Im, J.S.; Alves, P.M.; Martinet, O.; Halkic, N.; et al. Enrichment of Human Cd4+ V(Alpha)24/Vbeta11 Invariant Nkt Cells in Intrahepatic Malignant Tumors. J. Immunol. 2009, 182, 5140–5151. [Google Scholar] [CrossRef] [PubMed]
- Wolf, M.J.; Adili, A.; Piotrowitz, K.; Abdullah, Z.; Boege, Y.; Stemmer, K.; Ringelhan, M.; Simonavicius, N.; Egger, M.; Wohlleber, D.; et al. Metabolic Activation of Intrahepatic CD8+ T Cells and NKT Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes. Cancer Cell 2014, 26, 549–564. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, C.; Han, M.; Heinrich, B.; Fu, Q.; Zhang, Q.; Sandhu, M.; Agdashian, D.; Terabe, M.; Berzofsky, J.A.; Fako, V.; et al. Gut Microbiome-Mediated Bile Acid Metabolism Regulates Liver Cancer Via Nkt Cells. Science 2018, 360. [Google Scholar] [CrossRef] [PubMed]
- Janakiram, N.B.; Mohammed, A.; Bryant, T.; Ritchie, R.; Stratton, N.; Jackson, L.; Lightfoot, S.; Benbrook, D.M.; Asch, A.S.; Lang, M.L.; et al. Loss of Natural Killer T Cells Promotes Pancreatic Cancer in LSL-Kras(G12d/+) Mice. Immunology 2017, 152, 36–51. [Google Scholar] [CrossRef] [PubMed]
- Tachibana, T.; Onodera, H.; Tsuruyama, T.; Mori, A.; Nagayama, S.; Hiai, H.; Imamura, M. Increased Intratumor Valpha24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas. Clin. Cancer Res. 2005, 11, 7322–7327. [Google Scholar] [CrossRef]
- Wang, Y.; Sedimbi, S.; Lofbom, L.; Singh, A.K.; Porcelli, S.A.; Cardell, S.L. Unique Invariant Natural Killer T Cells Promote Intestinal Polyps by Suppressing Th1 Immunity and Promoting Regulatory T Cells. Mucosal Immunol. 2018, 11, 131–143. [Google Scholar] [CrossRef]
- Heller, F.; Fuss, I.J.; Nieuwenhuis, E.E.; Blumberg, R.S.; Strober, W. Oxazolone Colitis, a Th2 Colitis Model Resembling Ulcerative Colitis, Is Mediated by IL-13-Producing NK-T Cells. Immunity 2002, 17, 629–638. [Google Scholar] [CrossRef] [Green Version]
- Whiteside, T.L. The Role of Regulatory T Cells in Cancer Immunology. Immunotargets Ther. 2015, 4, 159–171. [Google Scholar] [CrossRef] [PubMed]
- Fu, J.; Zhang, Z.; Zhou, L.; Qi, Z.; Xing, S.; Lv, J.; Shi, J.; Fu, B.; Liu, Z.; Zhang, J.Y.; et al. Impairment of CD4+ Cytotoxic T Cells Predicts Poor Survival and High Recurrence Rates in Patients with Hepatocellular Carcinoma. Hepatology 2013, 58, 139–149. [Google Scholar] [CrossRef] [PubMed]
- Hwang, H.K.; Kim, H.I.; Kim, S.H.; Choi, J.; Kang, C.M.; Kim, K.S.; Lee, W.J. Prognostic Impact of the Tumor-Infiltrating Regulatory T-Cell (Foxp3(+))/Activated Cytotoxic T Lymphocyte (Granzyme B(+)) Ratio on Resected Left-Sided Pancreatic Cancer. Oncol. Lett. 2016, 12, 4477–4484. [Google Scholar] [CrossRef] [PubMed]
- Carreras, J.; Lopez-Guillermo, A.; Fox, B.C.; Colomo, L.; Martinez, A.; Roncador, G.; Montserrat, E.; Campo, E.; Banham, A.H. High Numbers of Tumor-Infiltrating Foxp3-Positive Regulatory T Cells Are Associated with Improved Overall Survival in Follicular Lymphoma. Blood 2006, 108, 2957–2964. [Google Scholar] [CrossRef]
- Frey, D.M.; Droeser, R.A.; Viehl, C.T.; Zlobec, I.; Lugli, A.; Zingg, U.; Oertli, D.; Kettelhack, C.; Terracciano, L.; Tornillo, L. High Frequency of Tumor-Infiltrating Foxp3(+) Regulatory T Cells Predicts Improved Survival in Mismatch Repair-Proficient Colorectal Cancer Patients. Int. J. Cancer 2010, 126, 2635–2643. [Google Scholar] [CrossRef] [PubMed]
- Wilke, C.M.; Wu, K.; Zhao, E.; Wang, G.; Zou, W. Prognostic Significance of Regulatory T Cells in Tumor. Int. J. Cancer 2010, 127, 748–758. [Google Scholar] [CrossRef]
- Akeus, P.; Langenes, V.; Kristensen, J.; von Mentzer, A.; Sparwasser, T.; Raghavan, S.; Quiding-Jarbrink, M. Treg-Cell Depletion Promotes Chemokine Production and Accumulation of CXCR3(+) Conventional T Cells in Intestinal Tumors. Eur. J. Immunol. 2015, 45, 1654–1666. [Google Scholar] [CrossRef] [PubMed]
- Blatner, N.R.; Mulcahy, M.F.; Dennis, K.L.; Scholtens, D.; Bentrem, D.J.; Phillips, J.D.; Ham, S.; Sandall, B.P.; Khan, M.W.; Mahvi, D.M.; et al. Expression of Rorgammat Marks a Pathogenic Regulatory T Cell Subset in Human Colon Cancer. Sci. Transl. Med. 2012, 4, 159. [Google Scholar] [CrossRef] [PubMed]
- Sefik, E.; Geva-Zatorsky, N.; Oh, S.; Konnikova, L.; Zemmour, D.; McGuire, A.M.; Burzyn, D.; Ortiz-Lopez, A.; Lobera, M.; Yang, J.; et al. Mucosal Immunology. Individual Intestinal Symbionts Induce a Distinct Population of ROR-gamma(+) Regulatory T Cells. Science 2015, 349, 993–997. [Google Scholar] [CrossRef]
- Kim, B.S.; Lu, H.; Ichiyama, K.; Chen, X.; Zhang, Y.B.; Mistry, N.A.; Tanaka, K.; Lee, Y.H.; Nurieva, R.; Zhang, L.; et al. Generation of Rorgammat(+) Antigen-Specific T Regulatory 17 Cells from Foxp3(+) Precursors in Autoimmunity. Cell Rep. 2017, 21, 195–207. [Google Scholar] [CrossRef]
- Becht, E.; de Reynies, A.; Giraldo, N.A.; Pilati, C.; Buttard, B.; Lacroix, L.; Selves, J.; Sautes-Fridman, C.; Laurent-Puig, P.; Fridman, W.H. Immune and Stromal Classification of Colorectal Cancer Is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy. Clin. Cancer Res. 2016, 22, 4057–4066. [Google Scholar] [CrossRef] [PubMed]
- Parker, J.S.; Mullins, M.; Cheang, M.C.; Leung, S.; Voduc, D.; Vickery, T.; Davies, S.; Fauron, C.; He, X.; Hu, Z.; et al. Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes. J. Clin. Oncol. 2009, 27, 1160–1167. [Google Scholar] [CrossRef] [PubMed]
- Guinney, J.; Dienstmann, R.; Wang, X.; de Reynies, A.; Schlicker, A.; Soneson, C.; Marisa, L.; Roepman, P.; Nyamundanda, G.; Angelino, P.; et al. The Consensus Molecular Subtypes of Colorectal Cancer. Nat. Med. 2015, 21, 1350–1356. [Google Scholar] [CrossRef] [PubMed]
- Kather, J.N.; Suarez-Carmona, M.; Charoentong, P.; Weis, C.A.; Hirsch, D.; Bankhead, P.; Horning, M.; Ferber, D.; Kel, I.; Herpel, E.; et al. Topography of Cancer-Associated Immune Cells in Human Solid Tumors. eLife 2018, 7. [Google Scholar] [CrossRef]
- Lanitis, E.; Dangaj, D.; Irving, M.; Coukos, G. Mechanisms Regulating T-Cell Infiltration and Activity in Solid Tumors. Ann. Oncol. 2017, 28, xii18–xii32. [Google Scholar] [CrossRef] [PubMed]
- Apolo, A.B.; Infante, J.R.; Balmanoukian, A.; Patel, M.R.; Wang, D.; Kelly, K.; Mega, A.E.; Britten, C.D.; Ravaud, A.; Mita, A.C.; et al. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, in Patients with Refractory Metastatic Urothelial Carcinoma: Results from a Multicenter, Phase Ib Study. J. Clin. Oncol. 2017, 35, 2117–2124. [Google Scholar] [CrossRef]
- Herbst, R.S.; Baas, P.; Kim, D.W.; Felip, E.; Perez-Gracia, J.L.; Han, J.Y.; Molina, J.; Kim, J.H.; Arvis, C.D.; Ahn, M.J.; et al. Pembrolizumab Versus Docetaxel for Previously Treated, PD-L1-Positive, Advanced Non-Small-Cell Lung Cancer (Keynote-010): A Randomised Controlled Trial. Lancet 2016, 387, 1540–1550. [Google Scholar] [CrossRef]
- Remon, J.; Besse, B.; Soria, J.C. Successes and Failures: What Did We Learn from Recent First-Line Treatment Immunotherapy Trials in Non-Small Cell Lung Cancer? BMC Med. 2017, 15, 55. [Google Scholar]
- Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M.M.; Ciuleanu, T.E.; Badin, F.; et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 376, 2415–2426. [Google Scholar] [CrossRef]
- Garon, E.B.; Rizvi, N.A.; Hui, R.; Leighl, N.; Balmanoukian, A.S.; Eder, J.P.; Patnaik, A.; Aggarwal, C.; Gubens, M.; Horn, L.; et al. Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 372, 2018–2028. [Google Scholar] [CrossRef]
- Gettinger, S.; Rizvi, N.A.; Chow, L.Q.; Borghaei, H.; Brahmer, J.; Ready, N.; Gerber, D.E.; Shepherd, F.A.; Antonia, S.; Goldman, J.W.; et al. Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2016, 34, 2980–2987. [Google Scholar] [CrossRef] [PubMed]
- Topalian, S.L.; Hodi, F.S.; Brahmer, J.R.; Gettinger, S.N.; Smith, D.C.; McDermott, D.F.; Powderly, J.D.; Carvajal, R.D.; Sosman, J.A.; Atkins, M.B.; et al. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. N. Engl. J. Med. 2012, 366, 2443–2454. [Google Scholar] [CrossRef] [PubMed]
- Hanna, G.J.; Lizotte, P.; Cavanaugh, M.; Kuo, F.C.; Shivdasani, P.; Frieden, A.; Chau, N.G.; Schoenfeld, J.D.; Lorch, J.H.; Uppaluri, R.; et al. Frameshift Events Predict Anti-PD-1/L1 Response in Head and Neck Cancer. JCI Insight 2018, 3. [Google Scholar] [CrossRef] [PubMed]
- Sunshine, J.; Taube, J.M. PD-1/PD-L1 Inhibitors. Curr. Opin. Pharmacol. 2015, 23, 32–38. [Google Scholar] [CrossRef] [PubMed]
- Weinberg, B.A.; Hameed, R.; Marshall, J.L. Biomarkers for Immune Therapy in Gastrointestinal Cancers. Clin. Adv. Hematol. Oncol. 2019, 17, 109–119. [Google Scholar]
- Havel, J.J.; Chowell, D.; Chan, T.A. The Evolving Landscape of Biomarkers for Checkpoint Inhibitor Immunotherapy. Nat. Rev. Cancer 2019, 19, 133–150. [Google Scholar] [CrossRef] [PubMed]
- Tang, H.; Liang, Y.; Anders, R.A.; Taube, J.M.; Qiu, X.; Mulgaonkar, A.; Liu, X.; Harrington, S.M.; Guo, J.; Xin, Y.; et al. Pd-L1 on Host Cells Is Essential for PD-L1 Blockade-Mediated Tumor Regression. J. Clin. Invest. 2018, 128, 580–588. [Google Scholar] [CrossRef] [PubMed]
- Chen, D.S.; Mellman, I. Elements of Cancer Immunity and the Cancer-Immune Set Point. Nature 2017, 541, 321–330. [Google Scholar] [CrossRef] [PubMed]
- Taylor, N.A.; Vick, S.C.; Iglesia, M.D.; Brickey, W.J.; Midkiff, B.R.; McKinnon, K.P.; Reisdorf, S.; Anders, C.K.; Carey, L.A.; Parker, J.S.; et al. Treg Depletion Potentiates Checkpoint Inhibition in Claudin-Low Breast Cancer. J. Clin. Invest. 2017, 127, 3472–3483. [Google Scholar] [CrossRef] [PubMed]
- Salem, M.E.; Xiu, J.; Weinberg, B.A.; El-Deiry, W.S.; Weiner, L.M.; Gatalica, Z.; Liu, Z.; Ghazaly, H.E.; Xiao, N.; Hwang, J.J.; et al. Characterization of Tumor Mutation Burden (TMB) in Gastrointestinal (Gi) Cancers. J. Clin. Oncol. 2017, 35, 530. [Google Scholar] [CrossRef]
- Chang, H.; Jung, W.; Kim, A.; Kim, H.K.; Kim, W.B.; Kim, J.H.; Kim, B.H. Expression and Prognostic Significance of Programmed Death Protein 1 and Programmed Death Ligand-1, and Cytotoxic T Lymphocyte-Associated Molecule-4 in Hepatocellular Carcinoma. APMIS 2017, 125, 690–698. [Google Scholar] [CrossRef] [PubMed]
- Liu, G.M.; Li, X.G.; Zhang, Y.M. Prognostic Role of PD-L1 for HCC Patients after Potentially Curative Resection: A Meta-Analysis. Cancer Cell Int. 2019, 19, 22. [Google Scholar] [CrossRef] [PubMed]
- Blando, J.; Sharma, A.; Higa, M.G.; Zhao, H.; Vence, L.; Yadav, S.S.; Kim, J.; Sepulveda, A.M.; Sharp, M.; Maitra, A.; et al. Comparison of Immune Infiltrates in Melanoma and Pancreatic Cancer Highlights Vista as a Potential Target in Pancreatic Cancer. Proc. Natl. Acad. Sci. USA 2019, 116, 1692–1697. [Google Scholar] [CrossRef] [PubMed]
- Salem, M.E.; Puccini, A.; Grothey, A.; Raghavan, D.; Goldberg, R.M.; Xiu, J.; Korn, W.M.; Weinberg, B.A.; Hwang, J.J.; Shields, A.F.; et al. Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers. Mol. Cancer Res. 2018, 16, 805–812. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buchhalter, I.; Rempel, E.; Endris, V.; Allgauer, M.; Neumann, O.; Volckmar, A.L.; Kirchner, M.; Leichsenring, J.; Lier, A.; von Winterfeld, M.; et al. Size Matters: Dissecting Key Parameters for Panel-Based Tumor Mutational Burden Analysis. Int. J. Cancer 2019, 144, 848–858. [Google Scholar] [CrossRef] [PubMed]
- Fabrizio, D.A.; George, T.J., Jr.; Dunne, R.F.; Frampton, G.; Sun, J.; Gowen, K.; Kennedy, M.; Greenbowe, J.; Schrock, A.B.; Hezel, A.F.; et al. Beyond Microsatellite Testing: Assessment of Tumor Mutational Burden Identifies Subsets of Colorectal Cancer Who May Respond to Immune Checkpoint Inhibition. J. Gastrointest Oncol. 2018, 9, 610–617. [Google Scholar] [CrossRef] [PubMed]
- Legrand, F.A.; Gandara, D.R.; Mariathasan, S.; Powles, T.; He, X.; Zhang, W.; Jhunjhunwala, S.; Nickles, D.; Bourgon, R.; Schleifman, E.; et al. Association of High Tissue TMB and Atezolizumab Efficacy across Multiple Tumor Types. J. Clin. Oncol. 2018, 36, 12000. [Google Scholar] [CrossRef]
- Balli, D.; Rech, A.J.; Stanger, B.Z.; Vonderheide, R.H. Immune Cytolytic Activity Stratifies Molecular Subsets of Human Pancreatic Cancer. Clin. Cancer Res. 2017, 23, 3129–3138. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Cancer Immunology. Mutational Landscape Determines Sensitivity to PD-1 Blockade in Non-Small Cell Lung Cancer. Science 2015, 348, 124–128. [Google Scholar] [CrossRef]
- Finotello, F.; Mayer, C.; Plattner, C.; Laschober, G.; Rieder, D.; Hackl, H.; Krogsdam, A.; Loncova, Z.; Posch, W.; Wilflingseder, D.; et al. Molecular and Pharmacological Modulators of the Tumor Immune Contexture Revealed by Deconvolution of RNA-Seq Data. Genome Med. 2019, 11, 34. [Google Scholar] [CrossRef]
- McGranahan, N.; Furness, A.J.; Rosenthal, R.; Ramskov, S.; Lyngaa, R.; Saini, S.K.; Jamal-Hanjani, M.; Wilson, G.A.; Birkbak, N.J.; Hiley, C.T.; et al. Clonal Neoantigens Elicit T Cell Immunoreactivity and Sensitivity to Immune Checkpoint Blockade. Science 2016, 351, 1463–1469. [Google Scholar] [CrossRef] [PubMed]
- Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Bartlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade. Science 2017, 357, 409–413. [Google Scholar] [CrossRef] [PubMed]
- Alexandrov, L.B.; Nik-Zainal, S.; Wedge, D.C.; Aparicio, S.A.; Behjati, S.; Biankin, A.V.; Bignell, G.R.; Bolli, N.; Borg, A.; Borresen-Dale, A.L.; et al. Signatures of Mutational Processes in Human Cancer. Nature 2013, 500, 415–421. [Google Scholar] [CrossRef] [PubMed]
- Long, J.; Wang, A.; Bai, Y.; Lin, J.; Yang, X.; Wang, D.; Yang, X.; Jiang, Y.; Zhao, H. Development and Validation of a TP53-Associated Immune Prognostic Model for Hepatocellular Carcinoma. EBioMedicine 2019, 42, 363–374. [Google Scholar] [CrossRef] [PubMed]
- Wormann, S.M.; Song, L.; Ai, J.; Diakopoulos, K.N.; Kurkowski, M.U.; Gorgulu, K.; Ruess, D.; Campbell, A.; Doglioni, C.; Jodrell, D.; et al. Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated with Patient Survival. Gastroenterology 2016, 151, 180–193. [Google Scholar] [CrossRef] [PubMed]
- Cooks, T.; Pateras, I.S.; Jenkins, L.M.; Patel, K.M.; Robles, A.I.; Morris, J.; Forshew, T.; Appella, E.; Gorgoulis, V.G.; Harris, C.C. Mutant P53 Cancers Reprogram Macrophages to Tumor Supporting Macrophages Via Exosomal mir-1246. Nat. Commun. 2018, 9, 771. [Google Scholar] [CrossRef] [PubMed]
- Dong, Z.Y.; Zhong, W.Z.; Zhang, X.C.; Su, J.; Xie, Z.; Liu, S.Y.; Tu, H.Y.; Chen, H.J.; Sun, Y.L.; Zhou, Q.; et al. Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma. Clin. Cancer Res. 2017, 23, 3012–3024. [Google Scholar] [CrossRef] [PubMed]
- Agersborg, S.; Jiang, S.; Chen, W.; Ma, W.; Albitar, M. PD-L1 Expression Correlation with TP53 Gene Mutation Status in Lung Cancer but Not in Colorectal Cancer. J. Clin. Oncol. 2016, 34, 11557. [Google Scholar] [CrossRef]
- Varchetta, V.; Montagnese, F.; Sibio, S.; Sica, G.; Muscaritoli, M.; Soda, G.; Giordano, G.; Brandi, R.; Tarsi, S.; Mancuso, G.; et al. PD-1/PD-L1 Expression and Regorafenib Clinical Efficacy on Refractory Pancreatic Cancer Patient. J. Clin. Oncol. 2016, 34, e15684. [Google Scholar] [CrossRef]
- Liao, W.; Overman, M.J.; Boutin, A.T.; Shang, X.; Zhao, D.; Dey, P.; Li, J.; Wang, G.; Lan, Z.; Li, J.; et al. KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer Cell 2019, 35, 559–572. [Google Scholar] [CrossRef]
- Atkins, D.; Breuckmann, A.; Schmahl, G.E.; Binner, P.; Ferrone, S.; Krummenauer, F.; Storkel, S.; Seliger, B. MHC Class I Antigen Processing Pathway Defects, RAS Mutations and Disease Stage in Colorectal Carcinoma. Int. J. Cancer 2004, 109, 265–273. [Google Scholar] [CrossRef] [PubMed]
- Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, D.R.; Steins, M.; Ready, N.E.; Chow, L.Q.; Vokes, E.E.; Felip, E.; Holgado, E.; et al. Nivolumab Versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 1627–1639. [Google Scholar] [CrossRef] [PubMed]
- Overman, M.J.; McDermott, R.; Leach, J.L.; Lonardi, S.; Lenz, H.J.; Morse, M.A.; Desai, J.; Hill, A.; Axelson, M.; Moss, R.A.; et al. Nivolumab in Patients with Metastatic DNA Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer (Checkmate 142): An Open-Label, Multicentre, Phase 2 Study. Lancet Oncol. 2017, 18, 1182–1191. [Google Scholar] [CrossRef]
- Sivan, A.; Corrales, L.; Hubert, N.; Williams, J.B.; Aquino-Michaels, K.; Earley, Z.M.; Benyamin, F.W.; Lei, Y.M.; Jabri, B.; Alegre, M.L.; et al. Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy. Science 2015, 350, 1084–1089. [Google Scholar] [CrossRef] [PubMed]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut Microbiome Modulates Response to Anti-PD-1 Immunotherapy in Melanoma Patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef]
- Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.P.M.; Alou, M.T.; Daillere, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; et al. Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy against Epithelial Tumors. Science 2018, 359, 91–97. [Google Scholar] [CrossRef] [PubMed]
- Vetizou, M.; Pitt, J.M.; Daillere, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P.; et al. Anticancer Immunotherapy by CTLA-4 Blockade Relies on the Gut Microbiota. Science 2015, 350, 1079–1084. [Google Scholar] [CrossRef] [PubMed]
- Hammarstrom, S. The Carcinoembryonic Antigen (Cea) Family: Structures, Suggested Functions and Expression in Normal and Malignant Tissues. Semin Cancer Biol. 1999, 9, 67–81. [Google Scholar] [CrossRef]
- Teng, D.; Wu, K.; Sun, Y.; Zhang, M.; Wang, D.; Wu, J.; Yin, T.; Gong, W.; Ding, Y.; Xiao, W.; et al. Significant Increased CA199 Levels in Acute Pancreatitis Patients Predicts the Presence of Pancreatic Cancer. Oncotarget 2018, 9, 12745–12753. [Google Scholar] [CrossRef]
- Maude, S.L.; Frey, N.; Shaw, P.A.; Aplenc, R.; Barrett, D.M.; Bunin, N.J.; Chew, A.; Gonzalez, V.E.; Zheng, Z.; Lacey, S.F.; et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N. Engl. J. Med. 2014, 371, 1507–1517. [Google Scholar] [CrossRef] [Green Version]
- Maude, S.L.; Laetsch, T.W.; Buechner, J.; Rives, S.; Boyer, M.; Bittencourt, H.; Bader, P.; Verneris, M.R.; Stefanski, H.E.; Myers, G.D.; et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 439–448. [Google Scholar] [CrossRef] [PubMed]
- Park, J.H.; Riviere, I.; Gonen, M.; Wang, X.; Senechal, B.; Curran, K.J.; Sauter, C.; Wang, Y.; Santomasso, B.; Mead, E.; et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 449–459. [Google Scholar] [CrossRef] [PubMed]
- Neelapu, S.S.; Locke, F.L.; Bartlett, N.L.; Lekakis, L.J.; Miklos, D.B.; Jacobson, C.A.; Braunschweig, I.; Oluwole, O.O.; Siddiqi, T.; Lin, Y.; et al. Axicabtagene Ciloleucel Car T-Cell Therapy in Refractory Large B-Cell Lymphoma. N. Engl. J. Med. 2017, 377, 2531–2544. [Google Scholar] [CrossRef] [PubMed]
- Moon, E.K.; Wang, L.C.; Dolfi, D.V.; Wilson, C.B.; Ranganathan, R.; Sun, J.; Kapoor, V.; Scholler, J.; Pure, E.; Milone, M.C.; et al. Multifactorial T-Cell Hypofunction That Is Reversible Can Limit the Efficacy of Chimeric Antigen Receptor-Transduced Human T Cells in Solid Tumors. Clin. Cancer Res. 2014, 20, 4262–4273. [Google Scholar] [CrossRef] [PubMed]
- Parente-Pereira, A.C.; Burnet, J.; Ellison, D.; Foster, J.; Davies, D.M.; van der Stegen, S.; Burbridge, S.; Chiapero-Stanke, L.; Wilkie, S.; Mather, S.; et al. Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in Scid Beige Mice. J. Clin. Immunol. 2011, 31, 710–718. [Google Scholar] [CrossRef] [PubMed]
- Kakarla, S.; Gottschalk, S. CAR T Cells for Solid Tumors: Armed and Ready to Go? Cancer J. 2014, 20, 151–155. [Google Scholar] [CrossRef] [PubMed]
- Park, J.R.; Digiusto, D.L.; Slovak, M.; Wright, C.; Naranjo, A.; Wagner, J.; Meechoovet, H.B.; Bautista, C.; Chang, W.C.; Ostberg, J.R.; et al. Adoptive Transfer of Chimeric Antigen Receptor Re-Directed Cytolytic T Lymphocyte Clones in Patients with Neuroblastoma. Mol. Ther. 2007, 15, 825–833. [Google Scholar] [CrossRef]
- Lamers, C.H.; Sleijfer, S.; van Steenbergen, S.; van Elzakker, P.; van Krimpen, B.; Groot, C.; Vulto, A.; den Bakker, M.; Oosterwijk, E.; Debets, R.; et al. Treatment of Metastatic Renal Cell Carcinoma with Caix CAR-Engineered T Cells: Clinical Evaluation and Management of on-Target Toxicity. Mol. Ther. 2013, 21, 904–912. [Google Scholar] [CrossRef]
- Tokarew, N.; Ogonek, J.; Endres, S.; von Bergwelt-Baildon, M.; Kobold, S. Teaching an Old Dog New Tricks: Next-Generation Car T Cells. Br. J. Cancer 2019, 120, 26–37. [Google Scholar] [CrossRef]
- Tahmasebi, S.; Elahi, R.; Esmaeilzadeh, A. Solid Tumors Challenges and New Insights of CAR T Cell Engineering. Stem. Cell Rev. 2019. [Google Scholar] [CrossRef]
- Martinez, M.; Moon, E.K. Car T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Front. Immunol. 2019, 10, 128. [Google Scholar] [CrossRef] [PubMed]
- Zhai, B.; Shi, D.; Gao, H.; Qi, X.; Jiang, H.; Zhang, Y.; Chi, J.; Ruan, H.; Wang, H.; Ru, Q.C.; et al. A Phase I Study of Anti-GPC3 Chimeric Antigen Receptor Modified T Cells (GPC3 CAR-T) in Chinese Patients with Refractory or Relapsed GPC3+ Hepatocellular Carcinoma (R/R GPC3+ Hcc). J. Clin. Oncol. 2017, 35, 3049. [Google Scholar] [CrossRef]
- Zhang, C.; Wang, Z.; Yang, Z.; Wang, M.; Li, S.; Li, Y.; Zhang, R.; Xiong, Z.; Wei, Z.; Shen, J.; et al. Phase I Escalating-Dose Trial of Car-T Therapy Targeting CEA(+) Metastatic Colorectal Cancers. Mol. Ther. 2017, 25, 1248–1258. [Google Scholar] [CrossRef] [PubMed]
- Feng, K.; Liu, Y.; Guo, Y.; Qiu, J.; Wu, Z.; Dai, H.; Yang, Q.; Wang, Y.; Han, W. Phase I Study of Chimeric Antigen Receptor Modified T Cells in Treating Her2-Positive Advanced Biliary Tract Cancers and Pancreatic Cancers. Protein Cell 2018, 9, 838–847. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Chen, M.; Wu, Z.; Tong, C.; Dai, H.; Guo, Y.; Liu, Y.; Huang, J.; Lv, H.; Luo, C.; et al. CD133-Directed Car T Cells for Advanced Metastasis Malignancies: A Phase I Trial. Oncoimmunology 2018, 7, e1440169. [Google Scholar] [CrossRef] [PubMed]
- Fukuoka, S.; Hara, H.; Takahashi, N.; Kojima, T.; Kawazoe, A.; Asayama, M.; Yoshii, T.; Kotani, D.; Tamura, H.; Mikamoto, Y.; et al. Regorafenib Plus Nivolumab in Patients with Advanced Gastric (Gc) or Colorectal Cancer (Crc): An Open-Label, Dose-Finding, and Dose-Expansion Phase 1b Trial (Regonivo, Epoc1603). J. Clin. Oncol. 2019, 37, 2522. [Google Scholar] [CrossRef]
- Eng, C.; Kim, T.W.; Bendell, J.; Argiles, G.; Tebbutt, N.C.; Di Bartolomeo, M.; Falcone, A.; Fakih, M.; Kozloff, M.; Segal, N.H.; et al. Atezolizumab with or without Cobimetinib Versus Regorafenib in Previously Treated Metastatic Colorectal Cancer (Imblaze370): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial. Lancet Oncol. 2019, 20, 849–861. [Google Scholar] [CrossRef]
- Adotevi, O.; Godet, Y.; Galaine, J.; Lakkis, Z.; Idirene, I.; Certoux, J.M.; Jary, M.; Loyon, R.; Laheurte, C.; Kim, S.; et al. In Situ Delivery of Allogeneic Natural Killer Cell (NK) Combined with Cetuximab in Liver Metastases of Gastrointestinal Carcinoma: A Phase I Clinical Trial. Oncoimmunology 2018, 7, e1424673. [Google Scholar] [CrossRef]
- Le, D.T.; Ko, A.H.; Wainberg, Z.A.; Picozzi, V.J.; Kindler, H.L.; Wang-Gillam, A.; Oberstein, P.E.; Morse, M.; Zeh, H.; Weekes, C.D.; et al. Results from a Phase 2b, Randomized, Multicenter Study of Gvax Pancreas and CRS-207 Compared to Chemotherapy in Adults with Previously-Treated Metastatic Pancreatic Adenocarcinoma (Eclipse Study). J. Clin. Oncol. 2017, 35, 345. [Google Scholar] [CrossRef]
- Kebenko, M.; Goebeler, M.E.; Wolf, M.; Hasenburg, A.; Seggewiss-Bernhardt, R.; Ritter, B.; Rautenberg, B.; Atanackovic, D.; Kratzer, A.; Rottman, J.B.; et al. A Multicenter Phase 1 Study of Solitomab (MT110, AMG 110), a Bispecific EPCAM/CD3 T-Cell Engager (Bite(R)) Antibody Construct, in Patients with Refractory Solid Tumors. Oncoimmunology 2018, 7, e1450710. [Google Scholar] [CrossRef]
- Bentebibel, S.E.; Hurwitz, M.E.; Bernatchez, C.; Haymaker, C.; Hudgens, C.W.; Kluger, H.M.; Tetzlaff, M.T.; Tagliaferri, M.A.; Zalevsky, J.; Hoch, U.; et al. A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel Il2rbetagamma-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discov. 2019, 9, 711–721. [Google Scholar] [CrossRef] [PubMed]
- Gomez-Roca, C.A.; Italiano, A.; Le Tourneau, C.; Cassier, P.A.; Toulmonde, M.; D’Angelo, S.P.; Campone, M.; Weber, K.L.; Loirat, D.; Cannarile, M.A.; et al. Phase I Study of Emactuzumab Single Agent or in Combination with Paclitaxel in Patients with Advanced/Metastatic Solid Tumors Reveals Depletion of Immunosuppressive M2-Like Macrophages. Ann. Oncol. 2019, 30, 1381–1392. [Google Scholar] [CrossRef]
- Liu, H.; Xu, Y.; Xiang, J.; Long, L.; Green, S.; Yang, Z.; Zimdahl, B.; Lu, J.; Cheng, N.; Horan, L.H.; et al. Targeting Alpha-Fetoprotein (AFP)-Mhc Complex with Car T-Cell Therapy for Liver Cancer. Clin. Cancer Res. 2017, 23, 478–488. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, S.A.; Yannelli, J.R.; Yang, J.C.; Topalian, S.L.; Schwartzentruber, D.J.; Weber, J.S.; Parkinson, D.R.; Seipp, C.A.; Einhorn, J.H.; White, D.E. Treatment of Patients with Metastatic Melanoma with Autologous Tumor-Infiltrating Lymphocytes and Interleukin 2. J. Natl. Cancer Inst. 1994, 86, 1159–1166. [Google Scholar] [CrossRef] [PubMed]
- Hinrichs, C.S.; Rosenberg, S.A. Exploiting the Curative Potential of Adoptive T-Cell Therapy for Cancer. Immunol. Rev. 2014, 257, 56–71. [Google Scholar] [CrossRef] [PubMed]
- Verdegaal, E.M. Adoptive Cell Therapy: A Highly Successful Individualized Therapy for Melanoma with Great Potential for Other Malignancies. Curr. Opin. Immunol. 2016, 39, 90–95. [Google Scholar] [CrossRef] [PubMed]
- Dudley, M.E.; Gross, C.A.; Langhan, M.M.; Garcia, M.R.; Sherry, R.M.; Yang, J.C.; Phan, G.Q.; Kammula, U.S.; Hughes, M.S.; Citrin, D.E.; et al. Cd8+ Enriched “Young” Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma. Clin. Cancer Res. 2010, 16, 6122–6131. [Google Scholar] [CrossRef] [PubMed]
- Yossef, R.; Tran, E.; Deniger, D.C.; Gros, A.; Pasetto, A.; Parkhurst, M.R.; Gartner, J.J.; Prickett, T.D.; Cafri, G.; Robbins, P.F.; et al. Enhanced Detection of Neoantigen-Reactive T Cells Targeting Unique and Shared Oncogenes for Personalized Cancer Immunotherapy. JCI Insight 2018, 3. [Google Scholar] [CrossRef] [PubMed]
- Deschoolmeester, V.; Baay, M.; Van Marck, E.; Weyler, J.; Vermeulen, P.; Lardon, F.; Vermorken, J.B. Tumor Infiltrating Lymphocytes: An Intriguing Player in the Survival of Colorectal Cancer Patients. BMC Immunol. 2010, 11, 19. [Google Scholar] [CrossRef] [PubMed]
- Geukes Foppen, M.H.; Donia, M.; Svane, I.M.; Haanen, J.B. Tumor-Infiltrating Lymphocytes for the Treatment of Metastatic Cancer. Mol. Oncol. 2015, 9, 1918–1935. [Google Scholar] [CrossRef] [PubMed]
- Tran, E.; Ahmadzadeh, M.; Lu, Y.C.; Gros, A.; Turcotte, S.; Robbins, P.F.; Gartner, J.J.; Zheng, Z.; Li, Y.F.; Ray, S.; et al. Immunogenicity of Somatic Mutations in Human Gastrointestinal Cancers. Science 2015, 350, 1387–1390. [Google Scholar] [CrossRef]
- Chen, T.H.; Zhang, Y.C.; Tan, Y.T.; An, X.; Xue, C.; Deng, Y.F.; Yang, W.; Yuan, X.; Shi, Y.X. Tumor-Infiltrating Lymphocytes Predict Prognosis of Breast Cancer Patients Treated with Anti-Her-2 Therapy. Oncotarget 2017, 8, 5219–5232. [Google Scholar] [CrossRef]
- Pruneri, G.; Gray, K.P.; Vingiani, A.; Viale, G.; Curigliano, G.; Criscitiello, C.; Lang, I.; Ruhstaller, T.; Gianni, L.; Goldhirsch, A.; et al. Tumor-Infiltrating Lymphocytes (TILS) Are a Powerful Prognostic Marker in Patients with Triple-Negative Breast Cancer Enrolled in the Ibcsg Phase III Randomized Clinical Trial 22-00. Breast Cancer Res. Treat. 2016, 158, 323–331. [Google Scholar] [CrossRef] [PubMed]
- Tran, E.; Turcotte, S.; Gros, A.; Robbins, P.F.; Lu, Y.C.; Dudley, M.E.; Wunderlich, J.R.; Somerville, R.P.; Hogan, K.; Hinrichs, C.S.; et al. Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer. Science 2014, 344, 641–645. [Google Scholar] [CrossRef] [PubMed]
- Tran, E.; Robbins, P.F.; Lu, Y.C.; Prickett, T.D.; Gartner, J.J.; Jia, L.; Pasetto, A.; Zheng, Z.; Ray, S.; Groh, E.M.; et al. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N. Engl. J. Med. 2016, 375, 2255–2262. [Google Scholar] [CrossRef] [Green Version]
- Cafri, G.; Yossef, R.; Pasetto, A.; Deniger, D.C.; Lu, Y.C.; Parkhurst, M.; Gartner, J.J.; Jia, L.; Ray, S.; Ngo, L.T.; et al. Memory T Cells Targeting Oncogenic Mutations Detected in Peripheral Blood of Epithelial Cancer Patients. Nat. Commun. 2019, 10, 449. [Google Scholar] [CrossRef] [PubMed]
- Malekzadeh, P.; Pasetto, A.; Robbins, P.F.; Parkhurst, M.R.; Paria, B.C.; Jia, L.; Gartner, J.J.; Hill, V.; Yu, Z.; Restifo, N.P.; et al. Neoantigen Screening Identifies Broad TP53 Mutant Immunogenicity in Patients with Epithelial Cancers. J. Clin. Invest. 2019, 129, 1109–1114. [Google Scholar] [CrossRef]
- Ahmadzadeh, M.; Johnson, L.A.; Heemskerk, B.; Wunderlich, J.R.; Dudley, M.E.; White, D.E.; Rosenberg, S.A. Tumor Antigen-Specific CD8 T Cells Infiltrating the Tumor Express High Levels of PD-1 and Are Functionally Impaired. Blood 2009, 114, 1537–1544. [Google Scholar] [CrossRef] [PubMed]
- Baitsch, L.; Baumgaertner, P.; Devevre, E.; Raghav, S.K.; Legat, A.; Barba, L.; Wieckowski, S.; Bouzourene, H.; Deplancke, B.; Romero, P.; et al. Exhaustion of Tumor-Specific CD8(+) T Cells in Metastases from Melanoma Patients. J. Clin. Invest. 2011, 121, 2350–2360. [Google Scholar] [CrossRef] [PubMed]
- Saito, H.; Okita, K.; Fusaki, N.; Sabel, M.S.; Chang, A.E.; Ito, F. Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells. Stem Cells Int. 2016, 2016, 8394960. [Google Scholar] [CrossRef]
- Rosenberg, S.A.; Tran, E.; Robbins, P.F. T-Cell Transfer Therapy Targeting Mutant KRAS. N. Engl. J. Med. 2017, 376, e11. [Google Scholar] [PubMed]
- Li, Q.Y.; Shi, Y.; Huang, D.H.; Yang, T.; Wang, J.H.; Yan, G.H.; Wang, H.Y.; Tang, X.J.; Xiao, C.Y.; Zhang, W.J.; et al. Cytokine-Induced Killer Cells Combined with Dendritic Cells Inhibited Liver Cancer Cells. Int. J. Clin. Exp. Med. 2015, 8, 5601–5610. [Google Scholar] [PubMed]
- He, W.; Huang, Z.; Zhou, S.; Huang, L.; Wang, B.; Zhu, L.; Ding, Y.; Yu, Y.L.; Zhang, S. The Effect of DC+CIK Combined Therapy on Rat Liver Cancer Model and Its Modulatory Effect on Immune Functions. Eur Rev. Med. Pharmacol. Sci. 2018, 22, 778–785. [Google Scholar]
- Zhang, J.; Li, H.; Gao, D.; Zhang, B.; Zheng, M.; Lun, M.; Wei, M.; Duan, R.; Guo, M.; Hua, J.; et al. A Prognosis and Impact Factor Analysis of DC-CIK Cell Therapy for Patients with Hepatocellular Carcinoma Undergoing Postoperative Tace. Cancer Biol. Ther. 2018, 19, 475–483. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Z.; Qin, H.; Weng, L.; Ni, Y. Clinical Efficacy of DC-CIK Combined with Sorafenib in the Treatment of Advanced Hepatocellular Carcinoma. J. BUON 2019, 24, 615–621. [Google Scholar] [PubMed]
- Zhu, H.; Yang, X.; Li, J.; Ren, Y.; Zhang, T.; Zhang, C.; Zhang, J.; Li, J.; Pang, Y. Immune Response, Safety, and Survival and Quality of Life Outcomes for Advanced Colorectal Cancer Patients Treated with Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Therapy. Biomed. Res. Int. 2014, 2014, 603871. [Google Scholar] [CrossRef] [PubMed]
- Gao, D.; Li, C.; Xie, X.; Zhao, P.; Wei, X.; Sun, W.; Liu, H.C.; Alexandrou, A.T.; Jones, J.; Zhao, R.; et al. Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy with Cytokine-Induced Killer Cells Improves Survival in Gastric and Colorectal Cancer Patients. PLoS ONE 2014, 9, e93886. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.S.; Kim, Y.G.; Park, E.J.; Kim, B.; Lee, H.K.; Hong, J.T.; Kim, Y.; Han, S.B. Cell-Based Immunotherapy for Colorectal Cancer with Cytokine-Induced Killer Cells. Immune. Netw. 2016, 16, 99–108. [Google Scholar] [CrossRef]
- Zhang, Y.; Zhang, X.; Zhang, A.; Li, K.; Qu, K. Clinical Applications of Dendritic Cells-Cytokine-Induced Killer Cells Mediated Immunotherapy for Pancreatic Cancer: An up-to-Date Meta-Analysis. Onco. Targets Ther. 2017, 10, 4173–4192. [Google Scholar] [CrossRef]
- Wang, Z.; Liu, Y.; Li, R.; Shang, Y.; Zhang, Y.; Zhao, L.; Li, W.; Yang, Y.; Zhang, X.; Yang, T.; et al. Autologous Cytokine-Induced Killer Cell Transfusion Increases Overall Survival in Advanced Pancreatic Cancer. J. Hematol. Oncol. 2016, 9, 6. [Google Scholar] [CrossRef]
- Lee, J.H.; Lee, J.H.; Lim, Y.S.; Yeon, J.E.; Song, T.J.; Yu, S.J.; Gwak, G.Y.; Kim, K.M.; Kim, Y.J.; Lee, J.W.; et al. Adjuvant Immunotherapy with Autologous Cytokine-Induced Killer Cells for Hepatocellular Carcinoma. Gastroenterology 2015, 148, 1383–1391. [Google Scholar] [CrossRef] [PubMed]
- Kellner, C.; Peipp, M.; Valerius, T. Effector Cell Recruitment by Bispecific Antibodies. In Bispecific Antibodies; Kontermann, R.E., Ed.; Springer: Berlin/Heidelberg, Germany, 2011; pp. 217–241. [Google Scholar]
- Kantarjian, H.; Stein, A.; Gokbuget, N.; Fielding, A.K.; Schuh, A.C.; Ribera, J.M.; Wei, A.; Dombret, H.; Foa, R.; Bassan, R.; et al. Blinatumomab Versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2017, 376, 836–847. [Google Scholar] [CrossRef] [PubMed]
- Moek, K.L.; Fiedler, W.M.; von Einem, J.C.; Verheul, H.M.; Seufferlein, T.; de Groot, D.J.; Heinemann, V.; Kebenko, M.; Menke-van der Houven van Oordt, C.W.; Ettrich, T.J.; et al. 427p phase I Study of Amg 211/Medi-565 Administered as Continuous Intravenous Infusion (CIV) for Relapsed/Refractory Gastrointestinal (Gi) Adenocarcinoma. Ann. Oncol. 2018, 29. [Google Scholar] [CrossRef]
- Dougan, M.; Dranoff, G.; Dougan, S.K. Cancer Immunotherapy: Beyond Checkpoint Blockade. Annu. Rev. Cancer Biol. 2019, 3, 55–75. [Google Scholar] [CrossRef]
- Kreiter, S.; Vormehr, M.; van de Roemer, N.; Diken, M.; Lower, M.; Diekmann, J.; Boegel, S.; Schrors, B.; Vascotto, F.; Castle, J.C.; et al. Mutant MHC Class II Epitopes Drive Therapeutic Immune Responses to Cancer. Nature 2015, 520, 692–696. [Google Scholar] [CrossRef]
- Stevanovic, S.; Pasetto, A.; Helman, S.R.; Gartner, J.J.; Prickett, T.D.; Howie, B.; Robins, H.S.; Robbins, P.F.; Klebanoff, C.A.; Rosenberg, S.A.; et al. Landscape of Immunogenic Tumor Antigens in Successful Immunotherapy of Virally Induced Epithelial Cancer. Science 2017, 356, 200–205. [Google Scholar] [CrossRef]
- Wong, K.K.; Li, W.A.; Mooney, D.J.; Dranoff, G. Advances in Therapeutic Cancer Vaccines. Adv. Immunol. 2016, 130, 191–249. [Google Scholar]
- Ott, P.A.; Hu, Z.; Keskin, D.B.; Shukla, S.A.; Sun, J.; Bozym, D.J.; Zhang, W.; Luoma, A.; Giobbie-Hurder, A.; Peter, L.; et al. An Immunogenic Personal Neoantigen Vaccine for Patients with Melanoma. Nature 2017, 547, 217–221. [Google Scholar] [CrossRef]
- Martin, S.D.; Brown, S.D.; Wick, D.A.; Nielsen, J.S.; Kroeger, D.R.; Twumasi-Boateng, K.; Holt, R.A.; Nelson, B.H. Low Mutation Burden in Ovarian Cancer May Limit the Utility of Neoantigen-Targeted Vaccines. PLoS ONE 2016, 11, e0155189. [Google Scholar] [CrossRef]
- Cappello, P.; Curcio, C.; Mandili, G.; Roux, C.; Bulfamante, S.; Novelli, F. Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination Is Seeking New Combo Partners. Cancers (Basel) 2018, 10, 51. [Google Scholar] [CrossRef]
- Snook, A.E.; Baybutt, T.R.; Xiang, B.; Abraham, T.S.; Flickinger, J.C., Jr.; Hyslop, T.; Zhan, T.; Kraft, W.K.; Sato, T.; Waldman, S.A. Split Tolerance Permits Safe Ad5-Gucy2c-Padre Vaccine-Induced T-Cell Responses in Colon Cancer Patients. J. Immunother. Cancer 2019, 7, 104. [Google Scholar] [CrossRef] [PubMed]
- Ablasser, A.; Goldeck, M.; Cavlar, T.; Deimling, T.; Witte, G.; Rohl, I.; Hopfner, K.P.; Ludwig, J.; Hornung, V. Cgas Produces a 2′–5′-Linked Cyclic Dinucleotide Second Messenger That Activates Sting. Nature 2013, 498, 380–384. [Google Scholar] [CrossRef] [PubMed]
- Chan, Y.K.; Gack, M.U. Viral Evasion of Intracellular DNA and Rna Sensing. Nat. Rev. Microbiol. 2016, 14, 360–373. [Google Scholar] [CrossRef] [PubMed]
- Hu, J.C.; Coffin, R.S.; Davis, C.J.; Graham, N.J.; Groves, N.; Guest, P.J.; Harrington, K.J.; James, N.D.; Love, C.A.; McNeish, I.; et al. A Phase I Study of Oncovex GM-CSF, a Second-Generation Oncolytic Herpes Simplex Virus Expressing Granulocyte Macrophage Colony-Stimulating Factor. Clin. Cancer Res. 2006, 12, 6737–6747. [Google Scholar] [CrossRef] [PubMed]
- Senzer, N.N.; Kaufman, H.L.; Amatruda, T.; Nemunaitis, M.; Reid, T.; Daniels, G.; Gonzalez, R.; Glaspy, J.; Whitman, E.; Harrington, K.; et al. Phase II Clinical Trial of a Granulocyte-Macrophage Colony-Stimulating Factor-Encoding, Second-Generation Oncolytic Herpesvirus in Patients with Unresectable Metastatic Melanoma. J. Clin. Oncol. 2009, 27, 5763–5771. [Google Scholar] [CrossRef] [PubMed]
- Harrington, K.J.; Andtbacka, R.H.; Collichio, F.; Downey, G.; Chen, L.; Szabo, Z.; Kaufman, H.L. Efficacy and Safety of Talimogene Laherparepvec Versus Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Stage III b/C and IVM1a Melanoma: Subanalysis of the Phase Iii Optim Trial. Onco. Targets Ther. 2016, 9, 7081–7093. [Google Scholar] [CrossRef] [PubMed]
- Andtbacka, R.H.I.; Collichio, F.; Harrington, K.J.; Middleton, M.R.; Downey, G.; hrling, K.; Kaufman, H.L. Final Analyses of Optim: A Randomized Phase III Trial of Talimogene Laherparepvec Versus Granulocyte-Macrophage Colony-Stimulating Factor in Unresectable Stage III-IV Melanoma. J. Immunother. Cancer 2019, 7, 145. [Google Scholar] [CrossRef]
- Chesney, J.; Puzanov, I.; Collichio, F.; Singh, P.; Milhem, M.M.; Glaspy, J.; Hamid, O.; Ross, M.; Friedlander, P.; Garbe, C.; et al. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination with Ipilimumab Versus Ipilimumab Alone in Patients with Advanced, Unresectable Melanoma. J. Clin. Oncol. 2018, 36, 1658–1667. [Google Scholar] [CrossRef]
- Hecht, J.R.; Bedford, R.; Abbruzzese, J.L.; Lahoti, S.; Reid, T.R.; Soetikno, R.M.; Kirn, D.H.; Freeman, S.M. A Phase I/II Trial of Intratumoral Endoscopic Ultrasound Injection of Onyx-015 with Intravenous Gemcitabine in Unresectable Pancreatic Carcinoma. Clin. Cancer Res. 2003, 9, 555–561. [Google Scholar]
- Samson, A.; Bentham, M.J.; Scott, K.; Nuovo, G.; Bloy, A.; Appleton, E.; Adair, R.A.; Dave, R.; Peckham-Cooper, A.; Toogood, G.; et al. Oncolytic Reovirus as a Combined Antiviral and Anti-Tumour Agent for the Treatment of Liver Cancer. Gut 2018, 67, 562–573. [Google Scholar] [CrossRef]
- Senzer, N.; Barve, M.; Kuhn, J.; Melnyk, A.; Beitsch, P.; Lazar, M.; Lifshitz, S.; Magee, M.; Oh, J.; Mill, S.W.; et al. Phase I Trial of “Bi-ShRNAi (Furin)/GMCSF DNA/Autologous Tumor Cell” Vaccine (FANG) in Advanced Cancer. Mol. Ther. 2012, 20, 679–686. [Google Scholar] [CrossRef]
- Zhang, H.; Li, K.; Lin, Y.; Xing, F.; Xiao, X.; Cai, J.; Zhu, W.; Liang, J.; Tan, Y.; Fu, L.; et al. Targeting Vcp Enhances Anticancer Activity of Oncolytic Virus M1 in Hepatocellular Carcinoma. Sci. Transl. Med. 2017, 9. [Google Scholar] [CrossRef]
- Royal, R.E.; Levy, C.; Turner, K.; Mathur, A.; Hughes, M.; Kammula, U.S.; Sherry, R.M.; Topalian, S.L.; Yang, J.C.; Lowy, I.; et al. Phase 2 Trial of Single Agent Ipilimumab (Anti-CTLA-4) for Locally Advanced or Metastatic Pancreatic Adenocarcinoma. J. Immunother. 2010, 33, 828–833. [Google Scholar] [CrossRef]
- Sangro, B.; Gomez-Martin, C.; de la Mata, M.; Inarrairaegui, M.; Garralda, E.; Barrera, P.; Riezu-Boj, J.I.; Larrea, E.; Alfaro, C.; Sarobe, P.; et al. A Clinical Trial of CTLA-4 Blockade with Tremelimumab in Patients with Hepatocellular Carcinoma and Chronic Hepatitis, C. J. Hepatol. 2013, 59, 81–88. [Google Scholar] [CrossRef]
- Topalian, S.L.; Drake, C.G.; Pardoll, D.M. Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy. Cancer Cell 2015, 27, 450–461. [Google Scholar] [CrossRef] [Green Version]
- Postow, M.A.; Callahan, M.K.; Wolchok, J.D. Immune Checkpoint Blockade in Cancer Therapy. J. Clin. Oncol. 2015, 33, 1974–1982. [Google Scholar] [CrossRef] [Green Version]
- Lupinacci, R.M.; Goloudina, A.; Buhard, O.; Bachet, J.B.; Marechal, R.; Demetter, P.; Cros, J.; Bardier-Dupas, A.; Collura, A.; Cervera, P.; et al. Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas. Gastroenterology 2018, 154, 1061–1065. [Google Scholar] [CrossRef]
- Mellman, I.; Hubbard-Lucey, V.M.; Tontonoz, M.J.; Kalos, M.D.; Chen, D.S.; Allison, J.P.; Drake, C.G.; Levitsky, H.; Lonberg, N.; van der Burg, S.H.; et al. De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute. Cancer Immunol. Res. 2016, 4, 279–288. [Google Scholar] [CrossRef]
- Baumeister, S.H.; Freeman, G.J.; Dranoff, G.; Sharpe, A.H. Coinhibitory Pathways in Immunotherapy for Cancer. Annu. Rev. Immunol. 2016, 34, 539–573. [Google Scholar] [CrossRef]
- Duffy, A.G.; Ulahannan, S.V.; Makorova-Rusher, O.; Rahma, O.; Wedemeyer, H.; Pratt, D.; Davis, J.L.; Hughes, M.S.; Heller, T.; ElGindi, M.; et al. Tremelimumab in Combination with Ablation in Patients with Advanced Hepatocellular Carcinoma. J. Hepatol. 2017, 66, 545–551. [Google Scholar] [CrossRef]
- Della Chiesa, M.; Pesce, S.; Muccio, L.; Carlomagno, S.; Sivori, S.; Moretta, A.; Marcenaro, E. Features of Memory-Like and PD-1(+) Human NK Cell Subsets. Front. Immunol 2016, 7, 351. [Google Scholar] [CrossRef]
- Benson, D.M., Jr.; Cohen, A.D.; Jagannath, S.; Munshi, N.C.; Spitzer, G.; Hofmeister, C.C.; Efebera, Y.A.; Andre, P.; Zerbib, R.; Caligiuri, M.A. A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma. Clin. Cancer Res. 2015, 21, 4055–4061. [Google Scholar] [CrossRef]
- Zaghi, E.; Calvi, M.; Marcenaro, E.; Mavilio, D.; Di Vito, C. Targeting NKG2A to Elucidate Natural Killer Cell Ontogenesis and to Develop Novel Immune-Therapeutic Strategies in Cancer Therapy. J. Leukoc. Biol. 2019, 105, 1243–1251. [Google Scholar] [CrossRef]
- Guillerey, C.; Huntington, N.D.; Smyth, M.J. Targeting Natural Killer Cells in Cancer Immunotherapy. Nat. Immunol. 2016, 17, 1025–1036. [Google Scholar] [CrossRef]
- Alnaggar, M.; Lin, M.; Mesmar, A.; Liang, S.; Qaid, A.; Xu, K.; Chen, J.; Niu, L.; Yin, Z. Allogenic Natural Killer Cell Immunotherapy Combined with Irreversible Electroporation for Stage IV Hepatocellular Carcinoma: Survival Outcome. Cell Physiol. Biochem. 2018, 48, 1882–1893. [Google Scholar] [CrossRef]
- Lin, M.; Alnaggar, M.; Liang, S.; Wang, X.; Liang, Y.; Zhang, M.; Chen, J.; Niu, L.; Xu, K. An Important Discovery on Combination of Irreversible Electroporation and Allogeneic Natural Killer Cell Immunotherapy for Unresectable Pancreatic Cancer. Oncotarget 2017, 8, 101795–101807. [Google Scholar] [CrossRef]
- Li, L.; Li, W.; Wang, C.; Yan, X.; Wang, Y.; Niu, C.; Zhang, X.; Li, M.; Tian, H.; Yao, C.; et al. Adoptive Transfer of Natural Killer Cells in Combination with Chemotherapy Improves Outcomes of Patients with Locally Advanced Colon Carcinoma. Cytotherapy 2018, 20, 134–148. [Google Scholar] [CrossRef]
- Ishikawa, T.; Okayama, T.; Sakamoto, N.; Ideno, M.; Oka, K.; Enoki, T.; Mineno, J.; Yoshida, N.; Katada, K.; Kamada, K.; et al. Phase I Clinical Trial of Adoptive Transfer of Expanded Natural Killer Cells in Combination with IGG1 Antibody in Patients with Gastric or Colorectal Cancer. Int. J. Cancer 2018, 142, 2599–2609. [Google Scholar] [CrossRef]
- Schonfeld, K.; Sahm, C.; Zhang, C.; Naundorf, S.; Brendel, C.; Odendahl, M.; Nowakowska, P.; Bonig, H.; Kohl, U.; Kloess, S.; et al. Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an Erbb2/Her2-Specific Chimeric Antigen Receptor. Mol. Ther. 2015, 23, 330–338. [Google Scholar] [CrossRef]
- Zhang, C.; Burger, M.C.; Jennewein, L.; Genssler, S.; Schonfeld, K.; Zeiner, P.; Hattingen, E.; Harter, P.N.; Mittelbronn, M.; Tonn, T.; et al. Erbb2/Her2-Specific NK Cells for Targeted Therapy of Glioblastoma. J. Natl. Cancer Inst. 2016, 108. [Google Scholar] [CrossRef]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Valkenburg, K.C.; de Groot, A.E.; Pienta, K.J. Targeting the Tumour Stroma to Improve Cancer Therapy. Nat. Rev. Clin. Oncol. 2018, 15, 366–381. [Google Scholar] [CrossRef] [PubMed]
- Ostermann, E.; Garin-Chesa, P.; Heider, K.H.; Kalat, M.; Lamche, H.; Puri, C.; Kerjaschki, D.; Rettig, W.J.; Adolf, G.R. Effective Immunoconjugate Therapy in Cancer Models Targeting a Serine Protease of Tumor Fibroblasts. Clin. Cancer Res. 2008, 14, 4584–4592. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- LeBeau, A.M.; Brennen, W.N.; Aggarwal, S.; Denmeade, S.R. Targeting the Cancer Stroma with a Fibroblast Activation Protein-Activated Promelittin Protoxin. Mol. Cancer Ther. 2009, 8, 1378–1386. [Google Scholar] [CrossRef] [PubMed]
- Kakarla, S.; Chow, K.K.; Mata, M.; Shaffer, D.R.; Song, X.T.; Wu, M.F.; Liu, H.; Wang, L.L.; Rowley, D.R.; Pfizenmaier, K.; et al. Antitumor Effects of Chimeric Receptor Engineered Human T Cells Directed to Tumor Stroma. Mol. Ther. 2013, 21, 1611–1620. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.C.; Lo, A.; Scholler, J.; Sun, J.; Majumdar, R.S.; Kapoor, V.; Antzis, M.; Cotner, C.E.; Johnson, L.A.; Durham, A.C.; et al. Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity. Cancer Immunol. Res. 2014, 2, 154–166. [Google Scholar] [CrossRef] [PubMed]
- Loeffler, M.; Kruger, J.A.; Niethammer, A.G.; Reisfeld, R.A. Targeting Tumor-Associated Fibroblasts Improves Cancer Chemotherapy by Increasing Intratumoral Drug Uptake. J. Clin. Invest. 2006, 116, 1955–1962. [Google Scholar] [CrossRef] [PubMed]
- Lo, A.; Wang, L.S.; Scholler, J.; Monslow, J.; Avery, D.; Newick, K.; O’Brien, S.; Evans, R.A.; Bajor, D.J.; Clendenin, C.; et al. Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells. Cancer Res. 2015, 75, 2800–2810. [Google Scholar] [CrossRef]
- Chen, M.; Xiang, R.; Wen, Y.; Xu, G.; Wang, C.; Luo, S.; Yin, T.; Wei, X.; Shao, B.; Liu, N.; et al. A Whole-Cell Tumor Vaccine Modified to Express Fibroblast Activation Protein Induces Antitumor Immunity against Both Tumor Cells and Cancer-Associated Fibroblasts. Sci. Rep. 2015, 5, 14421. [Google Scholar] [CrossRef]
- Mariathasan, S.; Turley, S.J.; Nickles, D.; Castiglioni, A.; Yuen, K.; Wang, Y.; Kadel, E.E., III; Koeppen, H.; Astarita, J.L.; Cubas, R.; et al. TGFbeta Attenuates Tumour Response to PD-L1 Blockade by Contributing to Exclusion of T Cells. Nature 2018, 554, 544–548. [Google Scholar] [CrossRef]
- Zhao, F.; Evans, K.; Xiao, C.; DeVito, N.; Theivanthiran, B.; Holtzhausen, A.; Siska, P.J.; Blobe, G.C.; Hanks, B.A. Stromal Fibroblasts Mediate Anti-PD-1 Resistance Via MMP-9 and Dictate TGF-beta Inhibitor Sequencing in Melanoma. Cancer Immunol. Res. 2018, 6, 1459–1471. [Google Scholar] [CrossRef] [PubMed]
- Pure, E. Seeking Synergy of Checkpoint Blockade through TGF-beta Inhibition. Cancer Immunol. Res. 2018, 6, 1444. [Google Scholar] [CrossRef] [PubMed]
- Ferrarelli, L.K. Combination Therapy Is a Game of Strategy. Sci. Signal. 2019, 12, eaaw5563. [Google Scholar] [CrossRef]
- Sanmamed, M.F.; Carranza-Rua, O.; Alfaro, C.; Onate, C.; Martin-Algarra, S.; Perez, G.; Landazuri, S.F.; Gonzalez, A.; Gross, S.; Rodriguez, I.; et al. Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins. Clin. Cancer Res. 2014, 20, 5697–5707. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dranoff, G. Cytokines in Cancer Pathogenesis and Cancer Therapy. Nat. Rev. Cancer 2004, 4, 11–22. [Google Scholar] [CrossRef] [PubMed]
- Del Vecchio, M.; Bajetta, E.; Canova, S.; Lotze, M.T.; Wesa, A.; Parmiani, G.; Anichini, A. Interleukin-12: Biological Properties and Clinical Application. Clin. Cancer Res. 2007, 13, 4677–4685. [Google Scholar] [CrossRef] [PubMed]
- Charych, D.H.; Hoch, U.; Langowski, J.L.; Lee, S.R.; Addepalli, M.K.; Kirk, P.B.; Sheng, D.; Liu, X.; Sims, P.W.; VanderVeen, L.A.; et al. NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin. Cancer Res. 2016, 22, 680–690. [Google Scholar] [CrossRef] [Green Version]
- Steele, C.W.; Karim, S.A.; Leach, J.D.G.; Bailey, P.; Upstill-Goddard, R.; Rishi, L.; Foth, M.; Bryson, S.; McDaid, K.; Wilson, Z.; et al. CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell 2016, 29, 832–845. [Google Scholar] [CrossRef] [Green Version]
- Ries, C.H.; Cannarile, M.A.; Hoves, S.; Benz, J.; Wartha, K.; Runza, V.; Rey-Giraud, F.; Pradel, L.P.; Feuerhake, F.; Klaman, I.; et al. Targeting Tumor-Associated Macrophages with Anti-CSF-1R Antibody Reveals a Strategy for Cancer Therapy. Cancer Cell 2014, 25, 846–859. [Google Scholar] [CrossRef] [Green Version]
- Zhao, Q. Dual Targeting of CCR2 and CCR5: Therapeutic Potential for Immunologic and Cardiovascular Diseases. J. Leukoc. Biol. 2010, 88, 41–55. [Google Scholar] [CrossRef]
- Neubert, N.J.; Schmittnaegel, M.; Bordry, N.; Nassiri, S.; Wald, N.; Martignier, C.; Tille, L.; Homicsko, K.; Damsky, W.; Maby-El Hajjami, H.; et al. T Cell-Induced CSF1 Promotes Melanoma Resistance to Pd1 Blockade. Sci. Transl. Med. 2018, 10, eaan3311. [Google Scholar] [CrossRef] [PubMed]
Cancer Type | Start Year | No of Participants | Site of Trial | Agents | Phase | Clinical Trials Gov Number | Recruitment Status |
---|---|---|---|---|---|---|---|
CAR-T Therapies | |||||||
Liver neoplasms | 2015 | 25 | China | EPCAM CAR-T cells | N/A | NCT02729493 | Yes |
Metastatic cancer | 2012 | 15 | US | Mesothelin CAR-T | I/II | NCT01583686 | Terminated |
HCC | 2018 | 50 | China | c-Met/PD-L1 CAR-T | Ia | NCT03672305 | Not yet |
Advanced HCC | 2015 | 13 | China | Anti-GPC3 CAR-T | I | NCT02395250 | Completed |
Malignancies | 2018 | 73 | China | Autologous CAR-T/TCR | I/II | NCT03638206 | Yes |
PC | 2017 | 18 | US | huCART-meso cells | I | NCT03323944 | Yes |
HCC | 2019 | 14 | US | GPC3-CAR-T + Cytoxan + Fludarabine | I | NCT02905188 | Yes |
Malignant solid tumor | 2019 | 30 | China | Nectin 4/FAP CAR-T | I | NCT03932565 | Yes |
PC | 2018 | 10 | China | CAR-T-meso cells | N/A | NCT03638193 | Yes |
PC CEA + liver metastases | 2019 | 6 | US | CAR2Anti-CEA CAR-T | Ib | NCT03818165 | Yes |
HCC/Metastatic colorectal and PC | 2016 | 20 | China | CAR-T | I/II | NCT02959151 | Unknown |
EPCAM + cancer | 2017 | 60 | China | CAR-T | I/II | NCT03013712 | Yes |
HCC | 2017 | 18 | China | ET1402L1-CAR-T | I | NCT03888859 | Yes |
Metastatic CRC | 2018 | 20 | China | EGFR/CAR-T | I | NCT03542799 | Not yet |
Advanced malignancies | 2015 | 20 | China | Anti-CD133 CAR-T | I | NCT02541370 | Unknown |
Tumor-Infiltrating Lymphocyte Therapies | |||||||
Metastatic cancer | 2010 | 332 | US | TIL + Aldesleukin + Cyclophosphamide + Fludarabine + Pembrolizumab | II | NCT01174121 | Yes |
Colorectal cancer | 2019 | 20 | China | Anti-PD-1 activated TIL + Xelox | I/II | NCT03904537 | Yes |
Advanced refractory solid tumor | 2017 | 40 | China | Neoantigen Reactive T Cells (NRTs) + PD-1 | I/II | NCT03171220 | Yes |
Advanced solid cancer | 2019 | 240 | US | TIL + Cyclophosphamide + Fludarabine | II | NCT03935893 | Not yet |
CIK Therapies | |||||||
PC | 2013 | 47 | China | DC/CIK + S1 | I/II | NCT01781520 | Completed |
PC | 2018 | 90 | China | CIK + Anti- CD3-MUC1 bispecific antibody | II | NCT03509298 | Yes |
CRC | 2012 | 46 | China | CIK + Folfox4 | IV | NCT03084809 | Completed |
Colon cancer | 2019 | 20 | Iran | Autologous CIK | I/II | NCT03329664 | Not yet |
Metastatic CRC | 2017 | 28 | Korea | Immuncell-LC | II | NCT03220984 | Enrolling by invitation |
HCC | 2015 | 55 | China | Autologous CIK | I/II | NCT03124498 | Unknown |
Resected liver cancer | 2008 | 200 | China | CIK | III | NCT00769106 | Completed |
Liver transplant in HCC | 2019 | 18 | Korea | Immuncell-LC | I/II | NCT03983967 | Yes |
iNKT Therapies | |||||||
Advanced solid tumor | 2017 | 40 | China | iNKT cells + CD8+ T cells | I/II | NCT03093688 | Yes |
HCC | 2017 | 18 | Adoptive iNKT therapy | I | NCT03175679 | Yes | |
Bispecific T cell engager | |||||||
PC | 2015 | 2 | US | anti-CD3 × anti-EGFR, IL-2 + GM-CSF | I/II | NCT02620865 | Active, NR |
Cancer Type | Immunotherapy | No of Participants | Phase | Clinical Outcome | Immune Response Adverse Effect | Reference |
---|---|---|---|---|---|---|
CAR-T | ||||||
HCC | Anti-GPC3 CAR-T | 13 | I | 1 PR, 3 SD, 2 PD | SAE grade 3 fever in 1 pt, 1 death | [282] |
CRC | CEA CAR-T | 10 | I | 7 SD, 2SD > 30 wk, 2 TS | No IrAE | [283] |
PC | HER2 CAR-T | 11 | I | PFS 4.8 months, 1PR, 5 SD | Reversible toxicities, mild to moderate | [284] |
Advanced metastatic cancer | CD133 CAR-T | 23 | I | PFS 5 months, 3PR, 14SD | Controllable toxicities | [285] |
Immune Checkpoint Inhibitor | ||||||
Advanced GC and CRC | Regorafenib +nivolumab | 50 | Ib | 38% ORR, 3PR in GC.44% RR(GC), 29% MSS(CRC) | Grade 3/4 toxicity in 17 pts | [286] |
CRC | Atezolizumab/+ or without cobimetinib versus regorafenib | 363 | III | mOS 8.87 months (combination group) | SEA in 40% of pts (combination group) | [287] |
NK Cell Therapy | ||||||
GI cancer | Allogenic NK therapy + Cetuximab | 9 | I | 2 SD, 1 PR, I DR | No DLT | [288] |
Cancer Vaccine | ||||||
Metastatic PC | G-VAX/CRS-207 | 93 | II | OS arm A 6.1 months vs. arm B 3.9 months | Grade 3/4 toxicity | [289] |
BiTES | ||||||
Refractory solid tumor | EpCAM/CD3 BiTES | 65 | I | 18 SD, 17 BR of SD, 28 PD, 1 unconfirmed PR | DLT in 15 pts, Grade 3/4 toxicity in 95% pts | [290] |
Stroma-Targeted Therapies | ||||||
PDAC | Pegylated IL-10 + Folfox | 353 | I/Ib | 15.5% ORR, 10.5% CR | Grade3/4 TrAEs, Grade 1/2 neuropathy | Ongoing |
Advanced metastatic solid tumor | NKTR-214 | 28 | I | SD in 14 pts, TR in 35% of pts | Grade 3 TrAE in 21.4% of pts | [291] |
Advanced metastatic solid tumor | Emactuzumab/ + paclitaxel | 217 | I | 7% ORR in combined therapy, no anti-tumor effect | No toxicity | [292] |
Cancer Type | Start Year | No of Participants | Site of Trial | Agents | Phase | ClinicalTrials.Gov Number | Recruitment Status |
---|---|---|---|---|---|---|---|
Immune Checkpoint Inhibitors/Combination Strategies | |||||||
Advanced metastatic solid tumor | 2018 | 48 | Japan | Regorafenib + nivolumab | I/II | NCT03406871 | Yes |
HCC | 2016 | 90 | US | Durvalumab + tremelimumab ablative therapies (TACE, RFA, cryoablation) | II | NCT02821754 | Yes |
MSS CRC | 2019 | 54 | US | Copanlisib + nivolumab | I/II | NCT03711058 | Yes |
MSI-H/dMMR or high TMB CRC | 2018 | 54 | China | PD-1 antibody + cox inhibitor | II | NCT03638297 | Yes |
Stage III&IV HCC | 2018 | 40 | US | Nivolumab + sorafenib | II | NCT03439891 | Yes |
CRC | 2018 | 74 | US | Anti-PD-L1/TGFbetaRII fusion protein M7824 | I/II | NCT03436563 | Yes |
Stage IV PC | 2019 | 40 | US | Nivolumab + cabiralizumab + gemcitabine | II | NCT03697564 | Not yet |
MSS CRC | 2019 | 64 | US | Nivolumab + relatlimab | II | NCT03642067 | Yes |
Advanced HCC | 2019 | 545 | AstraZeneca locations | Durvalumab + tremelimumab | II | NCT02519348 | Yes |
NK-Based Therapies | |||||||
CRC | 2018 | 54 | US | Allogenic NK + ALT803 (IL-15) | I | NCT02890758 | Yes |
Solid tumor | 2018 | 30 | China | NKG2D CAR-NK | I | NCT03415100 | Yes |
Relapse or refractory solid tumor | 2016 | 10 | China | Anti-MUC1 CAR-pNK | I/II | NCT02839954 | Unknown |
Cancer Vaccines | |||||||
Early and intermediate HCC | 2017 | 40 | Multiple locations | IMA970A + CV8102 adjuvant | I/II | NCT03203005 | Yes |
Refractory cancerCRC | 2017 | 35 | US | Pexa-Vec + durvalumab + tremelimumab | I/II | NCT03206073 | Yes |
PC | 2016 | 26 | US | LOAd703 oncolytic virus + gemcitabine + nab-paclitaxel | I/II | NCT02705196 | Yes |
Solid tumor | 2019 | 23 | US | VSV-IFNβ-NIS and pembrolizumab | I | NCT03647163 | Yes |
Colon cancer | 2012 | 3 | US | Autologous cancer vaccine TGF-β | II | NCT01505166 | Terminated |
Advanced malignant tumor | 2018 | 30 | China | iNeo-Vac-P01 | I | NCT03662815 | Yes |
CRC | 2005 | 37 | Taiwan | CEA pulsed dendriticcells | I/II | NCT00154713 | Unknown |
Stroma-Directed Therapies | |||||||
MSS CRC | 2018 | 20 | Germany | CCR5 inhibitor + pembrolizumab | I | NCT03274804 | Active, NR |
Malignant solid tumor | 2019 | 30 | China | Nectin 4/FAP CAR-T | I | NCT03932565 | Yes |
Advanced PDAC | 2019 | 30 | US | Nivolumab + CCR2/CCR5 dual antagonist + G-VAX | I/II | NCT03767582 | Not yet |
PC | 2008 | 12 | US | G-VAX vaccine + cyclophosphamide + pembrolizumab, + anti-CSF-1R monoclonal antibody IMC-CS4 | I | NCT03153410 | Yes |
Metastatic PC | 2017 | 566 | Multiple locations | Pegylated IL-10 + folfox | III | NCT02923921 | Yes |
PC | 2017 | 140 | US | Tocilizumab + gemcitabine+ nab-paclitaxel | II | NCT02767557 | Yes |
Metastatic PC | 2017 | 9 | US | IL-12 gene therapy | I | NCT03281382 | Yes |
HCC | 2018 | 35 | China | Chiauranib | 1 | NCT03245190 | Yes |
Advance cancer | 2018 | 280 | Multiple locations | Anti-IL-8 + Nivolumab | I/IIa | NCT03400332 | Yes |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Abolarinwa, B.A.; Ibrahim, R.B.; Huang, Y.-H. Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer. Int. J. Mol. Sci. 2019, 20, 4624. https://doi.org/10.3390/ijms20184624
Abolarinwa BA, Ibrahim RB, Huang Y-H. Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer. International Journal of Molecular Sciences. 2019; 20(18):4624. https://doi.org/10.3390/ijms20184624
Chicago/Turabian StyleAbolarinwa, Bilikis Aderonke, Ridwan Babatunde Ibrahim, and Yen-Hua Huang. 2019. "Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer" International Journal of Molecular Sciences 20, no. 18: 4624. https://doi.org/10.3390/ijms20184624