Contribution of Macrophages and T Cells in Skeletal Metastasis
Abstract
:1. Introduction
2. Macrophages
2.1. Role of Macrophages in Cancer
2.1.1. Tumor-Associated Macrophages in Tumor Progression and Metastasis
TAMs in Cancer Cell Proliferation
TAMs in Cancer Cell Invasion
TAMs in Angiogenesis
2.1.2. Role of Metastasis-Associated Macrophages in Metastatic Progression
2.1.3. Tumor-Associated Macrophages in Inflammation and Immunosuppression
2.1.4. Crosstalk between Macrophages and T-Cells in the Tumor Microenvironment
2.2. Role of Bone Microenvironment and Macrophages in Skeletal Metastasis
2.2.1. Bone Marrow-Derived Macrophages in Bone Metastasis
2.2.2. Contribution of Macrophage Efferocytosis in Bone Metastasis
2.3. Tumor-Associated Macrophages as Immunotargets and Their Potential Therapeutic Use in Bone Metastasis
3. Role of T Cells in Bone Metastasis
3.1. T Cells
3.2. Anti-Cancer Response of T Cells
3.3. Role of T Cells in Bone Metastasis, Friend or Foe
3.4. Effect of the Bone Metastatic Microenvironment on T Cells, Action-Reaction
3.4.1. Bone Marrow Mesenchymal Niches and Resident Memory T Cells
3.4.2. Cell- and Bone-Derived Transforming Growth Factor-β (TGF-β)
3.4.3. Myeloid-Derived Suppressor Cells
3.4.4. Hypoxia-Mediated Immunosuppression
3.5. T Cell-Directed Immunotherapies and Their Possible Use for the Treatment of Bone Metastases
3.5.1. γδT Cells and Nitrogen-Containing BPs
3.5.2. Immunotherapy Using Immune Checkpoint Inhibitors
3.5.3. Immunotherapy with Bispecific and Trispecific Antibodies
3.5.4. Engineering of T Cells for Cancer Therapy
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Fournier, P.G.; Chirgwin, J.M.; Guise, T.A. New insights into the role of T cells in the vicious cycle of bone metastases. Curr. Opin. Rheumatol. 2006, 18, 396–404. [Google Scholar] [CrossRef] [PubMed]
- Najafi, M.; Farhood, B.; Mortezaee, K. Contribution of regulatory T cells to cancer: A review. J. Cell Physiol. 2019, 234, 7983–7993. [Google Scholar] [CrossRef]
- Paolino, M.; Choidas, A.; Wallner, S.; Pranjic, B.; Uribesalgo, I.; Loeser, S.; Jamieson, A.M.; Langdon, W.Y.; Ikeda, F.; Fededa, J.P.; et al. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 2014, 507, 508–512. [Google Scholar] [CrossRef] [PubMed]
- Soki, F.N.; Cho, S.W.; Kim, Y.W.; Jones, J.D.; Park, S.I.; Koh, A.J.; Entezami, P.; Daignault-Newton, S.; Pienta, K.J.; Roca, H.; et al. Bone marrow macrophages support prostate cancer growth in bone. Oncotarget 2015, 6, 35782–35796. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sawant, A.; Ponnazhagan, S. Myeloid-derived suppressor cells as osteoclast progenitors: A novel target for controlling osteolytic bone metastasis. Cancer Res. 2013, 73, 4606–4610. [Google Scholar] [CrossRef] [Green Version]
- Capietto, A.H.; Faccio, R. Immune regulation of bone metastasis. Bonekey Rep. 2014, 3, 600. [Google Scholar] [CrossRef] [Green Version]
- Solinas, G.; Germano, G.; Mantovani, A.; Allavena, P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J. Leukoc. Biol. 2009, 86, 1065–1073. [Google Scholar] [CrossRef] [Green Version]
- Bingle, L.; Brown, N.J.; Lewis, C.E. The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. J. Pathol. 2002, 196, 254–265. [Google Scholar] [CrossRef]
- Wyckoff, J.B.; Wang, Y.; Lin, E.Y.; Li, J.F.; Goswami, S.; Stanley, E.R.; Segall, J.E.; Pollard, J.W.; Condeelis, J. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 2007, 67, 2649–2656. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Loberg, R.; Liao, J.; Ying, C.; Snyder, L.A.; Pienta, K.J.; McCauley, L.K. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone. Cancer Res. 2009, 69, 1685–1692. [Google Scholar] [CrossRef] [Green Version]
- Mantovani, A.; Sozzani, S.; Locati, M.; Allavena, P.; Sica, A. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002, 23, 549–555. [Google Scholar] [CrossRef]
- Mantovani, A.; Sica, A.; Sozzani, S.; Allavena, P.; Vecchi, A.; Locati, M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004, 25, 677–686. [Google Scholar] [CrossRef] [PubMed]
- Mosser, D.M.; Edwards, J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 2008, 8, 958–969. [Google Scholar] [CrossRef] [PubMed]
- Noy, R.; Pollard, J.W. Tumor-associated macrophages: From mechanisms to therapy. Immunity 2014, 41, 49–61. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chittezhath, M.; Dhillon, M.K.; Lim, J.Y.; Laoui, D.; Shalova, I.N.; Teo, Y.L.; Chen, J.; Kamaraj, R.; Raman, L.; Lum, J.; et al. Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 2014, 41, 815–829. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mendoza-Reinoso, V.; Baek, D.Y.; Kurutz, A.; Rubin, J.R.; Koh, A.J.; McCauley, L.K.; Roca, H. Unique Pro-Inflammatory Response of Macrophages during Apoptotic Cancer Cell Clearance. Cells 2020, 9, 429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kitamura, T.; Qian, B.Z.; Soong, D.; Cassetta, L.; Noy, R.; Sugano, G.; Kato, Y.; Li, J.; Pollard, J.W. CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages. J. Exp. Med. 2015, 212, 1043–1059. [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]
- 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. Investig. 2011, 121, 2350–2360. [Google Scholar] [CrossRef] [Green Version]
- 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] [Green Version]
- Boon, T.; Coulie, P.G.; Van den Eynde, B.J.; van der Bruggen, P. Human T cell responses against melanoma. Annu. Rev. Immunol. 2006, 24, 175–208. [Google Scholar] [CrossRef] [PubMed]
- Thommen, D.S.; Schreiner, J.; Muller, P.; Herzig, P.; Roller, A.; Belousov, A.; Umana, P.; Pisa, P.; Klein, C.; Bacac, M.; et al. Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors. Cancer Immunol. Res. 2015, 3, 1344–1355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mazo, I.B.; Honczarenko, M.; Leung, H.; Cavanagh, L.L.; Bonasio, R.; Weninger, W.; Engelke, K.; Xia, L.; McEver, R.P.; Koni, P.A.; et al. Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 2005, 22, 259–270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, D.; Hoffmann, P.; Lan, F.; Huie, P.; Higgins, J.; Strober, S. Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: Impact on allogeneic bone marrow transplantation. Blood 2002, 99, 1449–1457. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Perdiguero, E.G.; Klapproth, K.; Schulz, C.; Busch, K.; de Bruijn, M.; Rodewald, H.R.; Geissmann, F. The Origin of Tissue-Resident Macrophages: When an Erythro-myeloid Progenitor Is an Erythro-myeloid Progenitor. Immunity 2015, 43, 1023–1024. [Google Scholar] [CrossRef] [Green Version]
- Gomez Perdiguero, E.; Klapproth, K.; Schulz, C.; Busch, K.; Azzoni, E.; Crozet, L.; Garner, H.; Trouillet, C.; de Bruijn, M.F.; Geissmann, F.; et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 2015, 518, 547–551. [Google Scholar] [CrossRef]
- Takeya, M.; Komohara, Y. Role of tumor-associated macrophages in human malignancies: Friend or foe? Pathol. Int. 2016, 66, 491–505. [Google Scholar] [CrossRef]
- Franklin, R.A.; Liao, W.; Sarkar, A.; Kim, M.V.; Bivona, M.R.; Liu, K.; Pamer, E.G.; Li, M.O. The cellular and molecular origin of tumor-associated macrophages. Science 2014, 344, 921–925. [Google Scholar] [CrossRef] [Green Version]
- Qian, B.Z.; Li, J.; Zhang, H.; Kitamura, T.; Zhang, J.; Campion, L.R.; Kaiser, E.A.; Snyder, L.A.; Pollard, J.W. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011, 475, 222–225. [Google Scholar] [CrossRef] [Green Version]
- Cassetta, L.; Fragkogianni, S.; Sims, A.H.; Swierczak, A.; Forrester, L.M.; Zhang, H.; Soong, D.Y.H.; Cotechini, T.; Anur, P.; Lin, E.Y.; et al. Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets. Cancer Cell 2019, 35, 588–602.e510. [Google Scholar] [CrossRef] [Green Version]
- Movahedi, K.; Laoui, D.; Gysemans, C.; Baeten, M.; Stange, G.; Van den Bossche, J.; Mack, M.; Pipeleers, D.; In’t Veld, P.; De Baetselier, P.; et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010, 70, 5728–5739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sullivan, A.R.; Pixley, F.J. CSF-1R signaling in health and disease: A focus on the mammary gland. J. Mammary. Gland. Biol. Neoplasia 2014, 19, 149–159. [Google Scholar] [CrossRef] [PubMed]
- Loyher, P.L.; Hamon, P.; Laviron, M.; Meghraoui-Kheddar, A.; Goncalves, E.; Deng, Z.; Torstensson, S.; Bercovici, N.; Baudesson de Chanville, C.; Combadiere, B.; et al. Macrophages of distinct origins contribute to tumor development in the lung. J. Exp. Med. 2018, 215, 2536–2553. [Google Scholar] [CrossRef] [PubMed]
- Bowman, R.L.; Klemm, F.; Akkari, L.; Pyonteck, S.M.; Sevenich, L.; Quail, D.F.; Dhara, S.; Simpson, K.; Gardner, E.E.; Iacobuzio-Donahue, C.A.; et al. Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies. Cell Rep. 2016, 17, 2445–2459. [Google Scholar] [CrossRef] [Green Version]
- Zhu, Y.; Herndon, J.M.; Sojka, D.K.; Kim, K.W.; Knolhoff, B.L.; Zuo, C.; Cullinan, D.R.; Luo, J.; Bearden, A.R.; Lavine, K.J.; et al. Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression. Immunity 2017, 47, 323–338.e326. [Google Scholar] [CrossRef]
- Pollard, J.W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 2004, 4, 71–78. [Google Scholar] [CrossRef]
- Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature 2008, 454, 436–444. [Google Scholar] [CrossRef]
- Mantovani, A.; Marchesi, F.; Malesci, A.; Laghi, L.; Allavena, P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 2017, 14, 399–416. [Google Scholar] [CrossRef]
- Chang, M.K.; Raggatt, L.J.; Alexander, K.A.; Kuliwaba, J.S.; Fazzalari, N.L.; Schroder, K.; Maylin, E.R.; Ripoll, V.M.; Hume, D.A.; Pettit, A.R. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J. Immunol. 2008, 181, 1232–1244. [Google Scholar] [CrossRef] [Green Version]
- Wu, A.C.; Raggatt, L.J.; Alexander, K.A.; Pettit, A.R. Unraveling macrophage contributions to bone repair. Bonekey Rep. 2013, 2, 373. [Google Scholar] [CrossRef] [Green Version]
- Macedo, F.; Ladeira, K.; Pinho, F.; Saraiva, N.; Bonito, N.; Pinto, L.; Goncalves, F. Bone Metastases: An Overview. Oncol. Rev. 2017, 11, 321. [Google Scholar] [CrossRef]
- Sousa, S.; Maatta, J. The role of tumour-associated macrophages in bone metastasis. J. Bone Oncol. 2016, 5, 135–138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Battafarano, G.; Rossi, M.; Marampon, F.; Del Fattore, A. Cellular and Molecular Mediators of Bone Metastatic Lesions. Int. J. Mol. Sci. 2018, 19, 709. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roca, H.; Jones, J.D.; Purica, M.C.; Weidner, S.; Koh, A.J.; Kuo, R.; Wilkinson, J.E.; Wang, Y.; Daignault-Newton, S.; Pienta, K.J.; et al. Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone. J. Clin. Investig. 2018, 128, 248–266. [Google Scholar] [CrossRef] [PubMed]
- Soki, F.N.; Koh, A.J.; Jones, J.D.; Kim, Y.W.; Dai, J.; Keller, E.T.; Pienta, K.J.; Atabai, K.; Roca, H.; McCauley, L.K. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J. Biol. Chem. 2014, 289, 24560–24572. [Google Scholar] [CrossRef] [Green Version]
- Yang, M.; Liu, J.; Piao, C.; Shao, J.; Du, J. ICAM-1 suppresses tumor metastasis by inhibiting macrophage M2 polarization through blockade of efferocytosis. Cell Death Dis. 2015, 6, e1780. [Google Scholar] [CrossRef] [Green Version]
- Pollard, J.W. Trophic macrophages in development and disease. Nat. Rev. Immunol. 2009, 9, 259–270. [Google Scholar] [CrossRef] [Green Version]
- O’Sullivan, C.; Lewis, C.E.; Harris, A.L.; McGee, J.O. Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet 1993, 342, 148–149. [Google Scholar] [CrossRef]
- Yang, J.; Liao, D.; Chen, C.; Liu, Y.; Chuang, T.H.; Xiang, R.; Markowitz, D.; Reisfeld, R.A.; Luo, Y. Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells 2013, 31, 248–258. [Google Scholar] [CrossRef]
- Leek, R.D.; Hunt, N.C.; Landers, R.J.; Lewis, C.E.; Royds, J.A.; Harris, A.L. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J. Pathol. 2000, 190, 430–436. [Google Scholar] [CrossRef]
- Haque, A.; Moriyama, M.; Kubota, K.; Ishiguro, N.; Sakamoto, M.; Chinju, A.; Mochizuki, K.; Sakamoto, T.; Kaneko, N.; Munemura, R.; et al. CD206(+) tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production. Sci. Rep. 2019, 9, 14611. [Google Scholar] [CrossRef] [PubMed]
- Zeng, X.Y.; Xie, H.; Yuan, J.; Jiang, X.Y.; Yong, J.H.; Zeng, D.; Dou, Y.Y.; Xiao, S.S. M2-like tumor-associated macrophages-secreted EGF promotes epithelial ovarian cancer metastasis via activating EGFR-ERK signaling and suppressing lncRNA LIMT expression. Cancer Biol. Ther. 2019, 20, 956–966. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pinto, M.P.; Dye, W.W.; Jacobsen, B.M.; Horwitz, K.B. Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling. BMC Cancer 2014, 14, 735. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vignaud, J.M.; Marie, B.; Klein, N.; Plenat, F.; Pech, M.; Borrelly, J.; Martinet, N.; Duprez, A.; Martinet, Y. The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer. Cancer Res. 1994, 54, 5455–5463. [Google Scholar] [PubMed]
- Gocheva, V.; Wang, H.W.; Gadea, B.B.; Shree, T.; Hunter, K.E.; Garfall, A.L.; Berman, T.; Joyce, J.A. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010, 24, 241–255. [Google Scholar] [CrossRef] [Green Version]
- Yan, D.; Wang, H.W.; Bowman, R.L.; Joyce, J.A. STAT3 and STAT6 Signaling Pathways Synergize to Promote Cathepsin Secretion from Macrophages via IRE1alpha Activation. Cell Rep. 2016, 16, 2914–2927. [Google Scholar] [CrossRef] [Green Version]
- Dykes, S.S.; Fasanya, H.O.; Siemann, D.W. Cathepsin L secretion by host and neoplastic cells potentiates invasion. Oncotarget 2019, 10, 5560–5568. [Google Scholar] [CrossRef] [Green Version]
- Baghel, K.S.; Tewari, B.N.; Shrivastava, R.; Malik, S.A.; Lone, M.U.; Jain, N.K.; Tripathi, C.; Kanchan, R.K.; Dixit, S.; Singh, K.; et al. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1beta dependent upregulation of MYO3A gene in breast cancer cells. Oncoimmunology 2016, 5, e1196299. [Google Scholar] [CrossRef] [Green Version]
- Kleeff, J.; Kusama, T.; Rossi, D.L.; Ishiwata, T.; Maruyama, H.; Friess, H.; Buchler, M.W.; Zlotnik, A.; Korc, M. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. Int. J. Cancer 1999, 81, 650–657. [Google Scholar] [CrossRef]
- Kimsey, T.F.; Campbell, A.S.; Albo, D.; Wilson, M.; Wang, T.N. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J. 2004, 10, 374–380. [Google Scholar] [CrossRef]
- Steenbrugge, J.; Breyne, K.; Demeyere, K.; De Wever, O.; Sanders, N.N.; Van Den Broeck, W.; Colpaert, C.; Vermeulen, P.; Van Laere, S.; Meyer, E. Anti-inflammatory signaling by mammary tumor cells mediates prometastatic macrophage polarization in an innovative intraductal mouse model for triple-negative breast cancer. J. Exp. Clin. Cancer Res. 2018, 37, 191. [Google Scholar] [CrossRef]
- Zhang, Y.E. Non-Smad pathways in TGF-beta signaling. Cell Res. 2009, 19, 128–139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Derynck, R.; Akhurst, R.J. Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat. Cell Biol. 2007, 9, 1000–1004. [Google Scholar] [CrossRef] [PubMed]
- Massague, J. A very private TGF-beta receptor embrace. Mol. Cell 2008, 29, 149–150. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S.; Che, D.; Yang, F.; Chi, C.; Meng, H.; Shen, J.; Qi, L.; Liu, F.; Lv, L.; Li, Y.; et al. Tumor-associated macrophages promote tumor metastasis via the TGF-beta/SOX9 axis in non-small cell lung cancer. Oncotarget 2017, 8, 99801–99815. [Google Scholar] [CrossRef] [Green Version]
- Jung, H.; Bhangoo, S.; Banisadr, G.; Freitag, C.; Ren, D.; White, F.A.; Miller, R.J. Visualization of chemokine receptor activation in transgenic mice reveals peripheral activation of CCR2 receptors in states of neuropathic pain. J. Neurosci. 2009, 29, 8051–8062. [Google Scholar] [CrossRef] [Green Version]
- Fife, B.T.; Huffnagle, G.B.; Kuziel, W.A.; Karpus, W.J. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 2000, 192, 899–905. [Google Scholar] [CrossRef] [Green Version]
- Jimenez-Sainz, M.C.; Fast, B.; Mayor, F., Jr.; Aragay, A.M. Signaling pathways for monocyte chemoattractant protein 1-mediated extracellular signal-regulated kinase activation. Mol. Pharmacol. 2003, 64, 773–782. [Google Scholar] [CrossRef] [Green Version]
- Izumi, K.; Fang, L.Y.; Mizokami, A.; Namiki, M.; Li, L.; Lin, W.J.; Chang, C. Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Mol. Med. 2013, 5, 1383–1401. [Google Scholar] [CrossRef]
- Maolake, A.; Izumi, K.; Shigehara, K.; Natsagdorj, A.; Iwamoto, H.; Kadomoto, S.; Takezawa, Y.; Machioka, K.; Narimoto, K.; Namiki, M.; et al. Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis. Oncotarget 2017, 8, 9739–9751. [Google Scholar] [CrossRef] [Green Version]
- Lin, E.Y.; Nguyen, A.V.; Russell, R.G.; Pollard, J.W. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 2001, 193, 727–740. [Google Scholar] [CrossRef] [Green Version]
- Pixley, F.J.; Stanley, E.R. CSF-1 regulation of the wandering macrophage: Complexity in action. Trends Cell Biol. 2004, 14, 628–638. [Google Scholar] [CrossRef] [PubMed]
- Condeelis, J.; Singer, R.H.; Segall, J.E. The great escape: When cancer cells hijack the genes for chemotaxis and motility. Annu. Rev. Cell Dev. Biol. 2005, 21, 695–718. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamaguchi, H.; Pixley, F.; Condeelis, J. Invadopodia and podosomes in tumor invasion. Eur. J. Cell Biol. 2006, 85, 213–218. [Google Scholar] [CrossRef] [PubMed]
- Huang, S.; Van Arsdall, M.; Tedjarati, S.; McCarty, M.; Wu, W.; Langley, R.; Fidler, I.J. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J. Natl. Cancer Inst. 2002, 94, 1134–1142. [Google Scholar] [CrossRef] [PubMed]
- Du, R.; Lu, K.V.; Petritsch, C.; Liu, P.; Ganss, R.; Passegue, E.; Song, H.; Vandenberg, S.; Johnson, R.S.; Werb, Z.; et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 2008, 13, 206–220. [Google Scholar] [CrossRef] [Green Version]
- Lin, E.Y.; Li, J.F.; Gnatovskiy, L.; Deng, Y.; Zhu, L.; Grzesik, D.A.; Qian, H.; Xue, X.N.; Pollard, J.W. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006, 66, 11238–11246. [Google Scholar] [CrossRef] [Green Version]
- Halin, S.; Rudolfsson, S.H.; Van Rooijen, N.; Bergh, A. Extratumoral macrophages promote tumor and vascular growth in an orthotopic rat prostate tumor model. Neoplasia 2009, 11, 177–186. [Google Scholar] [CrossRef] [Green Version]
- Egami, K.; Murohara, T.; Shimada, T.; Sasaki, K.; Shintani, S.; Sugaya, T.; Ishii, M.; Akagi, T.; Ikeda, H.; Matsuishi, T.; et al. Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth. J. Clin. Investig. 2003, 112, 67–75. [Google Scholar] [CrossRef] [Green Version]
- Shieh, Y.S.; Hung, Y.J.; Hsieh, C.B.; Chen, J.S.; Chou, K.C.; Liu, S.Y. Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands. Ann. Surg. Oncol. 2009, 16, 751–760. [Google Scholar] [CrossRef]
- Espinosa, I.; Edris, B.; Lee, C.H.; Cheng, H.W.; Gilks, C.B.; Wang, Y.; Montgomery, K.D.; Varma, S.; Li, R.; Marinelli, R.J.; et al. CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis. Am. J. Pathol. 2011, 179, 2100–2107. [Google Scholar] [CrossRef] [PubMed]
- Wu, H.; Xu, J.B.; He, Y.L.; Peng, J.J.; Zhang, X.H.; Chen, C.Q.; Li, W.; Cai, S.R. Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer. J. Surg. Oncol. 2012, 106, 462–468. [Google Scholar] [CrossRef] [PubMed]
- Valkovic, T.; Dobrila, F.; Melato, M.; Sasso, F.; Rizzardi, C.; Jonjic, N. Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma. Virchows. Arch. 2002, 440, 583–588. [Google Scholar] [CrossRef] [PubMed]
- Hughes, R.; Qian, B.Z.; Rowan, C.; Muthana, M.; Keklikoglou, I.; Olson, O.C.; Tazzyman, S.; Danson, S.; Addison, C.; Clemons, M.; et al. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy. Cancer Res. 2015, 75, 3479–3491. [Google Scholar] [CrossRef] [Green Version]
- Osterberg, N.; Ferrara, N.; Vacher, J.; Gaedicke, S.; Niedermann, G.; Weyerbrock, A.; Doostkam, S.; Schaefer, H.E.; Plate, K.H.; Machein, M.R. Decrease of VEGF-A in myeloid cells attenuates glioma progression and prolongs survival in an experimental glioma model. Neuro. Oncol. 2016, 18, 939–949. [Google Scholar] [CrossRef] [Green Version]
- Yeo, E.J.; Cassetta, L.; Qian, B.Z.; Lewkowich, I.; Li, J.F.; Stefater, J.A., 3rd; Smith, A.N.; Wiechmann, L.S.; Wang, Y.; Pollard, J.W.; et al. Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res. 2014, 74, 2962–2973. [Google Scholar] [CrossRef] [Green Version]
- Werchau, S.; Toberer, F.; Enk, A.; Dammann, R.; Helmbold, P. Merkel cell carcinoma induces lymphatic microvessel formation. J. Am. Acad. Dermatol. 2012, 67, 215–225. [Google Scholar] [CrossRef]
- Qian, B.Z.; Pollard, J.W. Macrophage diversity enhances tumor progression and metastasis. Cell 2010, 141, 39–51. [Google Scholar] [CrossRef] [Green Version]
- Mazzieri, R.; Pucci, F.; Moi, D.; Zonari, E.; Ranghetti, A.; Berti, A.; Politi, L.S.; Gentner, B.; Brown, J.L.; Naldini, L.; et al. Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell 2011, 19, 512–526. [Google Scholar] [CrossRef] [Green Version]
- Weichand, B.; Popp, R.; Dziumbla, S.; Mora, J.; Strack, E.; Elwakeel, E.; Frank, A.C.; Scholich, K.; Pierre, S.; Syed, S.N.; et al. S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1beta. J. Exp. Med. 2017, 214, 2695–2713. [Google Scholar] [CrossRef]
- Doak, G.R.; Schwertfeger, K.L.; Wood, D.K. Distant Relations: Macrophage Functions in the Metastatic Niche. Trends Cancer 2018, 4, 445–459. [Google Scholar] [CrossRef]
- Argyle, D.; Kitamura, T. Targeting Macrophage-Recruiting Chemokines as a Novel Therapeutic Strategy to Prevent the Progression of Solid Tumors. Front. Immunol. 2018, 9, 2629. [Google Scholar] [CrossRef]
- Kitamura, T.; Doughty-Shenton, D.; Cassetta, L.; Fragkogianni, S.; Brownlie, D.; Kato, Y.; Carragher, N.; Pollard, J.W. Monocytes Differentiate to Immune Suppressive Precursors of Metastasis-Associated Macrophages in Mouse Models of Metastatic Breast Cancer. Front. Immunol. 2017, 8, 2004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qian, B.; Deng, Y.; Im, J.H.; Muschel, R.J.; Zou, Y.; Li, J.; Lang, R.A.; Pollard, J.W. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS ONE 2009, 4, e6562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Entenberg, D.; Rodriguez-Tirado, C.; Kato, Y.; Kitamura, T.; Pollard, J.W.; Condeelis, J. In vivo subcellular resolution optical imaging in the lung reveals early metastatic proliferation and motility. Intravital 2015, 4. [Google Scholar] [CrossRef] [PubMed]
- Chen, Q.; Zhang, X.H.; Massague, J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 2011, 20, 538–549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, D.; Joshi, N.; Choi, H.; Ryu, S.; Hahn, M.; Catena, R.; Sadik, H.; Argani, P.; Wagner, P.; Vahdat, L.T.; et al. Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res. 2012, 72, 1384–1394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rippaus, N.; Taggart, D.; Williams, J.; Andreou, T.; Wurdak, H.; Wronski, K.; Lorger, M. Metastatic site-specific polarization of macrophages in intracranial breast cancer metastases. Oncotarget 2016, 7, 41473–41487. [Google Scholar] [CrossRef] [Green Version]
- Bonapace, L.; Coissieux, M.M.; Wyckoff, J.; Mertz, K.D.; Varga, Z.; Junt, T.; Bentires-Alj, M. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 2014, 515, 130–133. [Google Scholar] [CrossRef]
- Freire Valls, A.; Knipper, K.; Giannakouri, E.; Sarachaga, V.; Hinterkopf, S.; Wuehrl, M.; Shen, Y.; Radhakrishnan, P.; Klose, J.; Ulrich, A.; et al. VEGFR1(+) Metastasis-Associated Macrophages Contribute to Metastatic Angiogenesis and Influence Colorectal Cancer Patient Outcome. Clin. Cancer Res. 2019, 25, 5674–5685. [Google Scholar] [CrossRef] [Green Version]
- Celus, W.; Di Conza, G.; Oliveira, A.I.; Ehling, M.; Costa, B.M.; Wenes, M.; Mazzone, M. Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis. Cell Rep. 2017, 21, 2842–2854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wan, S.G.; Taccioli, C.; Jiang, Y.; Chen, H.; Smalley, K.J.; Huang, K.; Liu, X.P.; Farber, J.L.; Croce, C.M.; Fong, L.Y. Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression. Int. J. Cancer 2011, 129, 331–345. [Google Scholar] [CrossRef] [PubMed]
- Ullman, T.A.; Itzkowitz, S.H. Intestinal inflammation and cancer. Gastroenterology 2011, 140, 1807–1816. [Google Scholar] [CrossRef] [PubMed]
- Engels, E.A. Inflammation in the development of lung cancer: Epidemiological evidence. Expert. Rev. Anticancer Ther. 2008, 8, 605–615. [Google Scholar] [CrossRef]
- Bromberg, J.; Wang, T.C. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009, 15, 79–80. [Google Scholar] [CrossRef] [Green Version]
- Grivennikov, S.; Karin, M. Autocrine IL-6 signaling: A key event in tumorigenesis? Cancer Cell 2008, 13, 7–9. [Google Scholar] [CrossRef] [Green Version]
- Chen, M.F.; Chen, P.T.; Lu, M.S.; Lin, P.Y.; Chen, W.C.; Lee, K.D. IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. Mol. Cancer 2013, 12, 26. [Google Scholar] [CrossRef] [Green Version]
- Guo, Y.; Xu, F.; Lu, T.; Duan, Z.; Zhang, Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat. Rev. 2012, 38, 904–910. [Google Scholar] [CrossRef]
- Zhao, G.; Zhu, G.; Huang, Y.; Zheng, W.; Hua, J.; Yang, S.; Zhuang, J.; Ye, J. IL-6 mediates the signal pathway of JAK-STAT3-VEGF-C promoting growth, invasion and lymphangiogenesis in gastric cancer. Oncol. Rep. 2016, 35, 1787–1795. [Google Scholar] [CrossRef] [Green Version]
- Che, D.; Zhang, S.; Jing, Z.; Shang, L.; Jin, S.; Liu, F.; Shen, J.; Li, Y.; Hu, J.; Meng, Q.; et al. Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/beta-catenin signalling pathway. Mol. Immunol. 2017, 90, 197–210. [Google Scholar] [CrossRef]
- Wan, S.; Zhao, E.; Kryczek, I.; Vatan, L.; Sadovskaya, A.; Ludema, G.; Simeone, D.M.; Zou, W.; Welling, T.H. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology 2014, 147, 1393–1404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, N.; Zhang, Y.; Zhang, X.; Lei, Z.; Hu, R.; Li, H.; Mao, Y.; Wang, X.; Irwin, D.M.; Niu, G.; et al. Exposure of tumor-associated macrophages to apoptotic MCF-7 cells promotes breast cancer growth and metastasis. Int. J. Mol. Sci. 2015, 16, 11966–11982. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dzaye, O.; Hu, F.; Derkow, K.; Haage, V.; Euskirchen, P.; Harms, C.; Lehnardt, S.; Synowitz, M.; Wolf, S.A.; Kettenmann, H. Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling. J. Neuropathol. Exp. Neurol. 2016, 75, 429–440. [Google Scholar] [CrossRef] [Green Version]
- Liu, C.Y.; Xu, J.Y.; Shi, X.Y.; Huang, W.; Ruan, T.Y.; Xie, P.; Ding, J.L. M2-polarized tumor-associated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab. Investig. 2013, 93, 844–854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fan, Q.M.; Jing, Y.Y.; Yu, G.F.; Kou, X.R.; Ye, F.; Gao, L.; Li, R.; Zhao, Q.D.; Yang, Y.; Lu, Z.H.; et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett. 2014, 352, 160–168. [Google Scholar] [CrossRef] [PubMed]
- Lewis, C.E.; Pollard, J.W. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006, 66, 605–612. [Google Scholar] [CrossRef] [Green Version]
- Herbst, R.S.; Soria, J.C.; Kowanetz, M.; Fine, G.D.; Hamid, O.; Gordon, M.S.; Sosman, J.A.; McDermott, D.F.; Powderly, J.D.; Gettinger, S.N.; et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515, 563–567. [Google Scholar] [CrossRef] [Green Version]
- Schultheis, A.M.; Scheel, A.H.; Ozretic, L.; George, J.; Thomas, R.K.; Hagemann, T.; Zander, T.; Wolf, J.; Buettner, R. PD-L1 expression in small cell neuroendocrine carcinomas. Eur. J. Cancer 2015, 51, 421–426. [Google Scholar] [CrossRef] [Green Version]
- Gordon, S.R.; Maute, R.L.; Dulken, B.W.; Hutter, G.; George, B.M.; McCracken, M.N.; Gupta, R.; Tsai, J.M.; Sinha, R.; Corey, D.; et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 2017, 545, 495–499. [Google Scholar] [CrossRef]
- Hartley, G.P.; Chow, L.; Ammons, D.T.; Wheat, W.H.; Dow, S.W. Programmed Cell Death Ligand 1 (PD-L1) Signaling Regulates Macrophage Proliferation and Activation. Cancer Immunol. Res. 2018, 6, 1260–1273. [Google Scholar] [CrossRef] [Green Version]
- Roux, C.; Jafari, S.M.; Shinde, R.; Duncan, G.; Cescon, D.W.; Silvester, J.; Chu, M.F.; Hodgson, K.; Berger, T.; Wakeham, A.; et al. Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1. Proc. Natl. Acad. Sci. USA 2019, 116, 4326–4335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wei, Y.; Zhao, Q.; Gao, Z.; Lao, X.M.; Lin, W.M.; Chen, D.P.; Mu, M.; Huang, C.X.; Liu, Z.Y.; Li, B.; et al. The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy. J. Clin. Investig. 2019, 129, 3347–3360. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sica, A.; Saccani, A.; Bottazzi, B.; Polentarutti, N.; Vecchi, A.; van Damme, J.; Mantovani, A. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J. Immunol. 2000, 164, 762–767. [Google Scholar] [CrossRef] [PubMed]
- Matsuda, M.; Salazar, F.; Petersson, M.; Masucci, G.; Hansson, J.; Pisa, P.; Zhang, Q.J.; Masucci, M.G.; Kiessling, R. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J. Exp. Med. 1994, 180, 2371–2376. [Google Scholar] [CrossRef] [Green Version]
- Wang, R.; Lu, M.; Zhang, J.; Chen, S.; Luo, X.; Qin, Y.; Chen, H. Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer. J. Exp. Clin. Cancer Res. 2011, 30, 62. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ruffell, B.; Chang-Strachan, D.; Chan, V.; Rosenbusch, A.; Ho, C.M.; Pryer, N.; Daniel, D.; Hwang, E.S.; Rugo, H.S.; Coussens, L.M. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 2014, 26, 623–637. [Google Scholar] [CrossRef] [Green Version]
- Mantovani, A.; Sica, A. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Curr. Opin. Immunol. 2010, 22, 231–237. [Google Scholar] [CrossRef]
- Standiford, T.J.; Kuick, R.; Bhan, U.; Chen, J.; Newstead, M.; Keshamouni, V.G. TGF-beta-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth. Oncogene 2011, 30, 2475–2484. [Google Scholar] [CrossRef] [Green Version]
- Zhang, F.; Wang, H.; Wang, X.; Jiang, G.; Liu, H.; Zhang, G.; Wang, H.; Fang, R.; Bu, X.; Cai, S.; et al. TGF-beta induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype. Oncotarget 2016, 7, 52294–52306. [Google Scholar] [CrossRef] [Green Version]
- Mantovani, A.; Allavena, P. The interaction of anticancer therapies with tumor-associated macrophages. J. Exp. Med. 2015, 212, 435–445. [Google Scholar] [CrossRef]
- Arlauckas, S.P.; Garren, S.B.; Garris, C.S.; Kohler, R.H.; Oh, J.; Pittet, M.J.; Weissleder, R. Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages. Theranostics 2018, 8, 5842–5854. [Google Scholar] [CrossRef] [PubMed]
- Prima, V.; Kaliberova, L.N.; Kaliberov, S.; Curiel, D.T.; Kusmartsev, S. COX2/mPGES1/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells. Proc. Natl. Acad. Sci. USA 2017, 114, 1117–1122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dunn, G.P.; Old, L.J.; Schreiber, R.D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21, 137–148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ugel, S.; De Sanctis, F.; Mandruzzato, S.; Bronte, V. Tumor-induced myeloid deviation: When myeloid-derived suppressor cells meet tumor-associated macrophages. J. Clin. Investig. 2015, 125, 3365–3376. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Biswas, S.K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat. Immunol. 2010, 11, 889–896. [Google Scholar] [CrossRef]
- 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] [Green Version]
- Sakaguchi, S. Regulatory T cells: Key controllers of immunologic self-tolerance. Cell 2000, 101, 455–458. [Google Scholar] [CrossRef] [Green Version]
- Liu, C.; Chikina, M.; Deshpande, R.; Menk, A.V.; Wang, T.; Tabib, T.; Brunazzi, E.A.; Vignali, K.M.; Sun, M.; Stolz, D.B.; et al. Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8(+) T Cell-Derived Interferon-gamma. Immunity 2019, 51, 381–397.e386. [Google Scholar] [CrossRef]
- Takenaka, M.C.; Gabriely, G.; Rothhammer, V.; Mascanfroni, I.D.; Wheeler, M.A.; Chao, C.C.; Gutierrez-Vazquez, C.; Kenison, J.; Tjon, E.C.; Barroso, A.; et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat. Neurosci. 2019, 22, 729–740. [Google Scholar] [CrossRef]
- Sinder, B.P.; Pettit, A.R.; McCauley, L.K. Macrophages: Their Emerging Roles in Bone. J. Bone Miner. Res. 2015, 30, 2140–2149. [Google Scholar] [CrossRef] [Green Version]
- Hernandez, R.K.; Wade, S.W.; Reich, A.; Pirolli, M.; Liede, A.; Lyman, G.H. Incidence of bone metastases in patients with solid tumors: Analysis of oncology electronic medical records in the United States. BMC Cancer 2018, 18, 44. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taube, T.; Elomaa, I.; Blomqvist, C.; Beneton, M.N.; Kanis, J.A. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. Bone 1994, 15, 161–166. [Google Scholar] [CrossRef]
- Southby, J.; Kissin, M.W.; Danks, J.A.; Hayman, J.A.; Moseley, J.M.; Henderson, M.A.; Bennett, R.C.; Martin, T.J. Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res. 1990, 50, 7710–7716. [Google Scholar] [PubMed]
- Kohno, N.; Kitazawa, S.; Sakoda, Y.; Kanbara, Y.; Furuya, Y.; Ohashi, O.; Kitazawa, R. Parathyroid Hormone-related Protein in Breast Cancer Tissues: Relationship between Primary and Metastatic Sites. Breast Cancer 1994, 1, 43–49. [Google Scholar] [CrossRef]
- Dougall, W.C.; Glaccum, M.; Charrier, K.; Rohrbach, K.; Brasel, K.; De Smedt, T.; Daro, E.; Smith, J.; Tometsko, M.E.; Maliszewski, C.R.; et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999, 13, 2412–2424. [Google Scholar] [CrossRef]
- Keller, E.T.; Zhang, J.; Cooper, C.R.; Smith, P.C.; McCauley, L.K.; Pienta, K.J.; Taichman, R.S. Prostate carcinoma skeletal metastases: Cross-talk between tumor and bone. Cancer Metastasis Rev. 2001, 20, 333–349. [Google Scholar] [CrossRef] [Green Version]
- Cullen, S.P.; Henry, C.M.; Kearney, C.J.; Logue, S.E.; Feoktistova, M.; Tynan, G.A.; Lavelle, E.C.; Leverkus, M.; Martin, S.J. Fas/CD95-induced chemokines can serve as "find-me" signals for apoptotic cells. Mol. Cell 2013, 49, 1034–1048. [Google Scholar] [CrossRef] [Green Version]
- Fadok, V.A.; Voelker, D.R.; Campbell, P.A.; Cohen, J.J.; Bratton, D.L.; Henson, P.M. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 1992, 148, 2207–2216. [Google Scholar]
- Borisenko, G.G.; Matsura, T.; Liu, S.X.; Tyurin, V.A.; Jianfei, J.; Serinkan, F.B.; Kagan, V.E. Macrophage recognition of externalized phosphatidylserine and phagocytosis of apoptotic Jurkat cells—existence of a threshold. Arch. Biochem. Biophys. 2003, 413, 41–52. [Google Scholar] [CrossRef]
- Poon, I.K.; Lucas, C.D.; Rossi, A.G.; Ravichandran, K.S. Apoptotic cell clearance: Basic biology and therapeutic potential. Nat. Rev. Immunol. 2014, 14, 166–180. [Google Scholar] [CrossRef] [Green Version]
- Bondanza, A.; Zimmermann, V.S.; Rovere-Querini, P.; Turnay, J.; Dumitriu, I.E.; Stach, C.M.; Voll, R.E.; Gaipl, U.S.; Bertling, W.; Poschl, E.; et al. Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J. Exp. Med. 2004, 200, 1157–1165. [Google Scholar] [CrossRef] [PubMed]
- Baghdadi, M.; Nagao, H.; Yoshiyama, H.; Akiba, H.; Yagita, H.; Dosaka-Akita, H.; Jinushi, M. Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Cancer Immunol. Immunother. 2013, 62, 629–637. [Google Scholar] [CrossRef] [PubMed]
- Cheng, L.; Ruan, Z. Tim-3 and Tim-4 as the potential targets for antitumor therapy. Hum. Vaccin. Immunother. 2015, 11, 2458–2462. [Google Scholar] [CrossRef] [PubMed]
- Sulciner, M.L.; Serhan, C.N.; Gilligan, M.M.; Mudge, D.K.; Chang, J.; Gartung, A.; Lehner, K.A.; Bielenberg, D.R.; Schmidt, B.; Dalli, J.; et al. Resolvins suppress tumor growth and enhance cancer therapy. J. Exp. Med. 2018, 215, 115–140. [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]
- Tap, W.D.; Wainberg, Z.A.; Anthony, S.P.; Ibrahim, P.N.; Zhang, C.; Healey, J.H.; Chmielowski, B.; Staddon, A.P.; Cohn, A.L.; Shapiro, G.I.; et al. Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N. Engl. J. Med. 2015, 373, 428–437. [Google Scholar] [CrossRef] [Green Version]
- Butowski, N.; Colman, H.; De Groot, J.F.; Omuro, A.M.; Nayak, L.; Wen, P.Y.; Cloughesy, T.F.; Marimuthu, A.; Haidar, S.; Perry, A.; et al. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: An Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro. Oncol. 2016, 18, 557–564. [Google Scholar] [CrossRef] [Green Version]
- Von Tresckow, B.; Morschhauser, F.; Ribrag, V.; Topp, M.S.; Chien, C.; Seetharam, S.; Aquino, R.; Kotoulek, S.; de Boer, C.J.; Engert, A. An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma. Clin. Cancer Res. 2015, 21, 1843–1850. [Google Scholar] [CrossRef] [Green Version]
- Edwards, D.K.t.; Watanabe-Smith, K.; Rofelty, A.; Damnernsawad, A.; Laderas, T.; Lamble, A.; Lind, E.F.; Kaempf, A.; Mori, M.; Rosenberg, M.; et al. CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells. Blood 2019, 133, 588–599. [Google Scholar] [CrossRef]
- 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]
- Cassier, P.A.; Italiano, A.; Gomez-Roca, C.A.; Le Tourneau, C.; Toulmonde, M.; Cannarile, M.A.; Ries, C.; Brillouet, A.; Muller, C.; Jegg, A.M.; et al. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: A dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015, 16, 949–956. [Google Scholar] [CrossRef]
- Hiraoka, K.; Zenmyo, M.; Watari, K.; Iguchi, H.; Fotovati, A.; Kimura, Y.N.; Hosoi, F.; Shoda, T.; Nagata, K.; Osada, H.; et al. Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci. 2008, 99, 1595–1602. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Knight, D.A.; Snyder, L.A.; Smyth, M.J.; Stewart, T.J. A role for CCL2 in both tumor progression and immunosurveillance. Oncoimmunology 2013, 2, e25474. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loberg, R.D.; Ying, C.; Craig, M.; Day, L.L.; Sargent, E.; Neeley, C.; Wojno, K.; Snyder, L.A.; Yan, L.; Pienta, K.J. Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo. Cancer Res. 2007, 67, 9417–9424. [Google Scholar] [CrossRef] [Green Version]
- Loberg, R.D.; Ying, C.; Craig, M.; Yan, L.; Snyder, L.A.; Pienta, K.J. CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia 2007, 9, 556–562. [Google Scholar] [CrossRef] [Green Version]
- Pienta, K.J.; Machiels, J.P.; Schrijvers, D.; Alekseev, B.; Shkolnik, M.; Crabb, S.J.; Li, S.; Seetharam, S.; Puchalski, T.A.; Takimoto, C.; et al. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Investig. New Drugs 2013, 31, 760–768. [Google Scholar] [CrossRef]
- Nywening, T.M.; Wang-Gillam, A.; Sanford, D.E.; Belt, B.A.; Panni, R.Z.; Cusworth, B.M.; Toriola, A.T.; Nieman, R.K.; Worley, L.A.; Yano, M.; et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: A single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016, 17, 651–662. [Google Scholar] [CrossRef] [Green Version]
- Huang, B.; Zhao, J.; Unkeless, J.C.; Feng, Z.H.; Xiong, H. TLR signaling by tumor and immune cells: A double-edged sword. Oncogene 2008, 27, 218–224. [Google Scholar] [CrossRef] [Green Version]
- Smits, E.L.; Ponsaerts, P.; Berneman, Z.N.; Van Tendeloo, V.F. The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 2008, 13, 859–875. [Google Scholar] [CrossRef] [Green Version]
- Ridnour, L.A.; Cheng, R.Y.; Switzer, C.H.; Heinecke, J.L.; Ambs, S.; Glynn, S.; Young, H.A.; Trinchieri, G.; Wink, D.A. Molecular pathways: Toll-like receptors in the tumor microenvironment—poor prognosis or new therapeutic opportunity. Clin. Cancer Res. 2013, 19, 1340–1346. [Google Scholar] [CrossRef] [Green Version]
- Shime, H.; Matsumoto, M.; Oshiumi, H.; Tanaka, S.; Nakane, A.; Iwakura, Y.; Tahara, H.; Inoue, N.; Seya, T. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors. Proc. Natl. Acad. Sci. USA 2012, 109, 2066–2071. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, L.; He, H.; Liang, R.; Yi, H.; Meng, X.; Chen, Z.; Pan, H.; Ma, Y.; Cai, L. ROS-Inducing Micelles Sensitize Tumor-Associated Macrophages to TLR3 Stimulation for Potent Immunotherapy. Biomacromolecules 2018, 19, 2146–2155. [Google Scholar] [CrossRef] [PubMed]
- Zanganeh, S.; Hutter, G.; Spitler, R.; Lenkov, O.; Mahmoudi, M.; Shaw, A.; Pajarinen, J.S.; Nejadnik, H.; Goodman, S.; Moseley, M.; et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotechnol. 2016, 11, 986–994. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.; Zhang, Z.; Xue, Y.; Wang, G.; Cheng, Y.; Pan, Y.; Zhao, S.; Hou, Y. Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I : C) promote melanoma regression. Theranostics 2018, 8, 6307–6321. [Google Scholar] [CrossRef] [PubMed]
- Thauvin, C.; Widmer, J.; Mottas, I.; Hocevar, S.; Allemann, E.; Bourquin, C.; Delie, F. Development of resiquimod-loaded modified PLA-based nanoparticles for cancer immunotherapy: A kinetic study. Eur. J. Pharm. Biopharm. 2019, 139, 253–261. [Google Scholar] [CrossRef] [Green Version]
- Huang, L.; Xu, H.; Peng, G. TLR-mediated metabolic reprogramming in the tumor microenvironment: Potential novel strategies for cancer immunotherapy. Cell Mol. Immunol. 2018, 15, 428–437. [Google Scholar] [CrossRef] [Green Version]
- Smith, D.A.; Conkling, P.; Richards, D.A.; Nemunaitis, J.J.; Boyd, T.E.; Mita, A.C.; de La Bourdonnaye, G.; Wages, D.; Bexon, A.S. Antitumor activity and safety of combination therapy with the Toll-like receptor 9 agonist IMO-2055, erlotinib, and bevacizumab in advanced or metastatic non-small cell lung cancer patients who have progressed following chemotherapy. Cancer Immunol. Immunother. 2014, 63, 787–796. [Google Scholar] [CrossRef]
- Zhang, F.; Parayath, N.N.; Ene, C.I.; Stephan, S.B.; Koehne, A.L.; Coon, M.E.; Holland, E.C.; Stephan, M.T. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat. Commun. 2019, 10, 3974. [Google Scholar] [CrossRef]
- Cai, X.; Yin, Y.; Li, N.; Zhu, D.; Zhang, J.; Zhang, C.Y.; Zen, K. Re-polarization of tumor-associated macrophages to pro-inflammatory M1 macrophages by microRNA-155. J. Mol. Cell Biol. 2012, 4, 341–343. [Google Scholar] [CrossRef]
- Liu, R.; Wei, H.; Gao, P.; Yu, H.; Wang, K.; Fu, Z.; Ju, B.; Zhao, M.; Dong, S.; Li, Z.; et al. CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis. Oncotarget 2017, 8, 39021–39032. [Google Scholar] [CrossRef] [Green Version]
- Weiskopf, K.; Jahchan, N.S.; Schnorr, P.J.; Cristea, S.; Ring, A.M.; Maute, R.L.; Volkmer, A.K.; Volkmer, J.P.; Liu, J.; Lim, J.S.; et al. CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J. Clin. Investig. 2016, 126, 2610–2620. [Google Scholar] [CrossRef] [PubMed]
- Sikic, B.I.; Lakhani, N.; Patnaik, A.; Shah, S.A.; Chandana, S.R.; Rasco, D.; Colevas, A.D.; O’Rourke, T.; Narayanan, S.; Papadopoulos, K.; et al. First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients with Advanced Cancers. J. Clin. Oncol. 2019, 37, 946–953. [Google Scholar] [CrossRef]
- Petrova, P.S.; Viller, N.N.; Wong, M.; Pang, X.; Lin, G.H.; Dodge, K.; Chai, V.; Chen, H.; Lee, V.; House, V.; et al. TTI-621 (SIRPalphaFc): A CD47-Blocking Innate Immune Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin. Cancer Res. 2017, 23, 1068–1079. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vonderheide, R.H.; Flaherty, K.T.; Khalil, M.; Stumacher, M.S.; Bajor, D.L.; Hutnick, N.A.; Sullivan, P.; Mahany, J.J.; Gallagher, M.; Kramer, A.; et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol. 2007, 25, 876–883. [Google Scholar] [CrossRef] [PubMed]
- Vonderheide, R.H.; Burg, J.M.; Mick, R.; Trosko, J.A.; Li, D.; Shaik, M.N.; Tolcher, A.W.; Hamid, O. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology 2013, 2, e23033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beatty, G.L.; Torigian, D.A.; Chiorean, E.G.; Saboury, B.; Brothers, A.; Alavi, A.; Troxel, A.B.; Sun, W.; Teitelbaum, U.R.; Vonderheide, R.H.; et al. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin. Cancer Res. 2013, 19, 6286–6295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Charo, I.F.; Taubman, M.B. Chemokines in the pathogenesis of vascular disease. Circ. Res. 2004, 95, 858–866. [Google Scholar] [CrossRef] [Green Version]
- Lebrecht, A.; Grimm, C.; Lantzsch, T.; Ludwig, E.; Hefler, L.; Ulbrich, E.; Koelbl, H. Monocyte chemoattractant protein-1 serum levels in patients with breast cancer. Tumour. Biol. 2004, 25, 14–17. [Google Scholar] [CrossRef]
- Lu, Y.; Chen, Q.; Corey, E.; Xie, W.; Fan, J.; Mizokami, A.; Zhang, J. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clin. Exp. Metastasis 2009, 26, 161–169. [Google Scholar] [CrossRef]
- Herroon, M.K.; Rajagurubandara, E.; Rudy, D.L.; Chalasani, A.; Hardaway, A.L.; Podgorski, I. Macrophage cathepsin K promotes prostate tumor progression in bone. Oncogene 2013, 32, 1580–1593. [Google Scholar] [CrossRef] [Green Version]
- Fend, L.; Accart, N.; Kintz, J.; Cochin, S.; Reymann, C.; Le Pogam, F.; Marchand, J.B.; Menguy, T.; Slos, P.; Rooke, R.; et al. Therapeutic effects of anti-CD115 monoclonal antibody in mouse cancer models through dual inhibition of tumor-associated macrophages and osteoclasts. PLoS ONE 2013, 8, e73310. [Google Scholar] [CrossRef] [Green Version]
- Okuda, H.; Kobayashi, A.; Xia, B.; Watabe, M.; Pai, S.K.; Hirota, S.; Xing, F.; Liu, W.; Pandey, P.R.; Fukuda, K.; et al. Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells. Cancer Res. 2012, 72, 537–547. [Google Scholar] [CrossRef] [Green Version]
- Roca, H.; McCauley, L.K. Efferocytosis and prostate cancer skeletal metastasis: Implications for intervention. Oncoscience 2018, 5, 174–176. [Google Scholar] [CrossRef]
- Li, Y.; Yin, Y.; Mariuzza, R.A. Structural and biophysical insights into the role of CD4 and CD8 in T cell activation. Front. Immunol. 2013, 4, 206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Luckheeram, R.V.; Zhou, R.; Verma, A.D.; Xia, B. CD4(+)T cells: Differentiation and functions. Clin. Dev. Immunol. 2012, 2012, 925135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, N.; Bevan, M.J. CD8(+) T cells: Foot soldiers of the immune system. Immunity 2011, 35, 161–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mittrucker, H.W.; Visekruna, A.; Huber, M. Heterogeneity in the differentiation and function of CD8(+) T cells. Arch. Immunol. Ther. Exp. 2014, 62, 449–458. [Google Scholar] [CrossRef]
- Pauza, C.D.; Liou, M.L.; Lahusen, T.; Xiao, L.; Lapidus, R.G.; Cairo, C.; Li, H. Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local. Front. Immunol. 2018, 9, 1305. [Google Scholar] [CrossRef]
- Lo Presti, E.; Pizzolato, G.; Corsale, A.M.; Caccamo, N.; Sireci, G.; Dieli, F.; Meraviglia, S. gammadelta T Cells and Tumor Microenvironment: From Immunosurveillance to Tumor Evasion. Front. Immunol. 2018, 9, 1395. [Google Scholar] [CrossRef] [PubMed]
- Schreiber, K.; Karrison, T.G.; Wolf, S.P.; Kiyotani, K.; Steiner, M.; Littmann, E.R.; Pamer, E.G.; Kammertoens, T.; Schreiber, H.; Leisegang, M. Impact of TCR Diversity on the Development of Transplanted or Chemically Induced Tumors. Cancer Immunol. Res. 2020, 8, 192–202. [Google Scholar] [CrossRef] [PubMed]
- Sethna, Z.; Elhanati, Y.; Dudgeon, C.S.; Callan, C.G., Jr.; Levine, A.J.; Mora, T.; Walczak, A.M. Insights into immune system development and function from mouse T-cell repertoires. Proc. Natl. Acad. Sci. USA 2017, 114, 2253–2258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xing, Y.; Hogquist, K.A. T-cell tolerance: Central and peripheral. Cold. Spring. Harb. Perspect. Biol. 2012, 4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kandoth, C.; McLellan, M.D.; Vandin, F.; Ye, K.; Niu, B.; Lu, C.; Xie, M.; Zhang, Q.; McMichael, J.F.; Wyczalkowski, M.A.; et al. Mutational landscape and significance across 12 major cancer types. Nature 2013, 502, 333–339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr.; Kinzler, K.W. Cancer genome landscapes. Science 2013, 339, 1546–1558. [Google Scholar] [CrossRef]
- Efremova, M.; Finotello, F.; Rieder, D.; Trajanoski, Z. Neoantigens Generated by Individual Mutations and Their Role in Cancer Immunity and Immunotherapy. Front. Immunol. 2017, 8, 1679. [Google Scholar] [CrossRef] [Green Version]
- Zapatka, M.; Borozan, I.; Brewer, D.S.; Iskar, M.; Grundhoff, A.; Alawi, M.; Desai, N.; Sültmann, H.; Moch, H.; Alawi, M.; et al. The landscape of viral associations in human cancers. Nat. Genet. 2020. [Google Scholar] [CrossRef] [Green Version]
- Fogg, M.H.; Wirth, L.J.; Posner, M.; Wang, F. Decreased EBNA-1-specific CD8+ T cells in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Proc. Natl. Acad. Sci. USA 2009, 106, 3318–3323. [Google Scholar] [CrossRef] [Green Version]
- Stevanovic, S.; Draper, L.M.; Langhan, M.M.; Campbell, T.E.; Kwong, M.L.; Wunderlich, J.R.; Dudley, M.E.; Yang, J.C.; Sherry, R.M.; Kammula, U.S.; et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J. Clin. Oncol. 2015, 33, 1543–1550. [Google Scholar] [CrossRef] [Green Version]
- Traversari, C.; van der Bruggen, P.; Van den Eynde, B.; Hainaut, P.; Lemoine, C.; Ohta, N.; Old, L.; Boon, T. Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. ImmunoGenetics 1992, 35, 145–152. [Google Scholar] [CrossRef]
- Chen, D.S.; Mellman, I. Oncology meets immunology: The cancer-immunity cycle. Immunity 2013, 39, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Chan, M.S.; Wang, L.; Felizola, S.J.; Ueno, T.; Toi, M.; Loo, W.; Chow, L.W.; Suzuki, T.; Sasano, H. Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients—An immunohistochemical study of Cd8+ and Foxp3+ using double immunostaining with correlation to the pathobiological response of the patients. Int. J. Biol. Markers 2012, 27, e295–e304. [Google Scholar] [CrossRef]
- Denkert, C.; Wienert, S.; Poterie, A.; Loibl, S.; Budczies, J.; Badve, S.; Bago-Horvath, Z.; Bane, A.; Bedri, S.; Brock, J.; et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: Results of the ring studies of the international immuno-oncology biomarker working group. Mod. Pathol. 2016, 29, 1155–1164. [Google Scholar] [CrossRef]
- Svennevig, J.L.; Lunde, O.C.; Holter, J.; Bjorgsvik, D. Lymphoid infiltration and prognosis in colorectal carcinoma. Br. J. Cancer 1984, 49, 375–377. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Conejo-Garcia, J.R.; Katsaros, D.; Gimotty, P.A.; Massobrio, M.; Regnani, G.; Makrigiannakis, A.; Gray, H.; Schlienger, K.; Liebman, M.N.; et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med. 2003, 348, 203–213. [Google Scholar] [CrossRef] [Green Version]
- An, X.; Romain, G.; Martinez-Paniagua, M.; Bandey, I.N.; Adolacion, J.R.T.; Fathi, M.; Liadi, I.; Sadeghi, F.; Mahendra, A.; Amritkar, A.; et al. CAR+ T cell anti-tumor efficacy revealed by multi-dimensional single-cell profiling. J. Immunol. 2019, 202, 134-2. [Google Scholar]
- Merouane, A.; Rey-Villamizar, N.; Lu, Y.; Liadi, I.; Romain, G.; Lu, J.; Singh, H.; Cooper, L.J.; Varadarajan, N.; Roysam, B. Automated profiling of individual cell-cell interactions from high-throughput time-lapse imaging microscopy in nanowell grids (TIMING). Bioinformatics 2015, 31, 3189–3197. [Google Scholar] [CrossRef] [Green Version]
- Ahrends, T.; Spanjaard, A.; Pilzecker, B.; Babala, N.; Bovens, A.; Xiao, Y.; Jacobs, H.; Borst, J. CD4(+) T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness. Immunity 2017, 47, 848–861.e845. [Google Scholar] [CrossRef] [Green Version]
- Borst, J.; Ahrends, T.; Babala, N.; Melief, C.J.M.; Kastenmuller, W. CD4(+) T cell help in cancer immunology and immunotherapy. Nat. Rev. Immunol. 2018, 18, 635–647. [Google Scholar] [CrossRef]
- Gil Del Alcazar, C.R.; Huh, S.J.; Ekram, M.B.; Trinh, A.; Liu, L.L.; Beca, F.; Zi, X.; Kwak, M.; Bergholtz, H.; Su, Y.; et al. Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition. Cancer Discov. 2017, 7, 1098–1115. [Google Scholar] [CrossRef] [Green Version]
- Koebel, C.M.; Vermi, W.; Swann, J.B.; Zerafa, N.; Rodig, S.J.; Old, L.J.; Smyth, M.J.; Schreiber, R.D. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007, 450, 903–907. [Google Scholar] [CrossRef]
- Mittal, D.; Gubin, M.M.; Schreiber, R.D.; Smyth, M.J. New insights into cancer immunoediting and its three component phases—Elimination, equilibrium and escape. Curr. Opin. Immunol. 2014, 27, 16–25. [Google Scholar] [CrossRef] [Green Version]
- Han, B.S.; Ji, S.; Woo, S.; Lee, J.H.; Sin, J.I. Regulation of the translation activity of antigen-specific mRNA is responsible for antigen loss and tumor immune escape in a HER2-expressing tumor model. Sci. Rep. 2019, 9, 2855. [Google Scholar] [CrossRef]
- Jager, E.; Ringhoffer, M.; Karbach, J.; Arand, M.; Oesch, F.; Knuth, A. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: Evidence for immunoselection of antigen-loss variants in vivo. Int. J. Cancer 1996, 66, 470–476. [Google Scholar] [CrossRef]
- Dance, A. Cancer immunotherapy comes of age. Science 2017, 355, 1220–1222. [Google Scholar] [CrossRef] [Green Version]
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [Green Version]
- Okhrimenko, A.; Grun, J.R.; Westendorf, K.; Fang, Z.; Reinke, S.; von Roth, P.; Wassilew, G.; Kuhl, A.A.; Kudernatsch, R.; Demski, S.; et al. Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory. Proc. Natl. Acad. Sci. USA 2014, 111, 9229–9234. [Google Scholar] [CrossRef] [Green Version]
- Tokoyoda, K.; Zehentmeier, S.; Hegazy, A.N.; Albrecht, I.; Grun, J.R.; Lohning, M.; Radbruch, A. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity 2009, 30, 721–730. [Google Scholar] [CrossRef] [Green Version]
- Becker, T.C.; Coley, S.M.; Wherry, E.J.; Ahmed, R. Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. J. Immunol. 2005, 174, 1269–1273. [Google Scholar] [CrossRef]
- Feuerer, M.; Rocha, M.; Bai, L.; Umansky, V.; Solomayer, E.F.; Bastert, G.; Diel, I.J.; Schirrmacher, V. Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients. Int. J. Cancer 2001, 92, 96–105. [Google Scholar] [CrossRef]
- Feuerer, M.; Beckhove, P.; Bai, L.; Solomayer, E.F.; Bastert, G.; Diel, I.J.; Pedain, C.; Oberniedermayr, M.; Schirrmacher, V.; Umansky, V. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat. Med. 2001, 7, 452–458. [Google Scholar] [CrossRef]
- Schuetz, F.; Ehlert, K.; Ge, Y.; Schneeweiss, A.; Rom, J.; Inzkirweli, N.; Sohn, C.; Schirrmacher, V.; Beckhove, P. Treatment of advanced metastasized breast cancer with bone marrow-derived tumour-reactive memory T cells: A pilot clinical study. Cancer Immunol. Immunother. 2009, 58, 887–900. [Google Scholar] [CrossRef] [PubMed]
- Martini, M.; Testi, M.G.; Pasetto, M.; Picchio, M.C.; Innamorati, G.; Mazzocco, M.; Ugel, S.; Cingarlini, S.; Bronte, V.; Zanovello, P.; et al. IFN-gamma-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer. Vaccine 2010, 28, 3548–3557. [Google Scholar] [CrossRef]
- Kakuta, S.; Tagawa, Y.; Shibata, S.; Nanno, M.; Iwakura, Y. Inhibition of B16 melanoma experimental metastasis by interferon-gamma through direct inhibition of cell proliferation and activation of antitumour host mechanisms. Immunology 2002, 105, 92–100. [Google Scholar] [CrossRef]
- Xu, Z.; Hurchla, M.A.; Deng, H.; Uluckan, O.; Bu, F.; Berdy, A.; Eagleton, M.C.; Heller, E.A.; Floyd, D.H.; Dirksen, W.P.; et al. Interferon-gamma targets cancer cells and osteoclasts to prevent tumor-associated bone loss and bone metastases. J. Biol. Chem. 2009, 284, 4658–4666. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sato, K.; Suematsu, A.; Okamoto, K.; Yamaguchi, A.; Morishita, Y.; Kadono, Y.; Tanaka, S.; Kodama, T.; Akira, S.; Iwakura, Y.; et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J. Exp. Med. 2006, 203, 2673–2682. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hong, S.; Qian, J.; Yang, J.; Li, H.; Kwak, L.W.; Yi, Q. Roles of idiotype-specific t cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth. Cancer Res. 2008, 68, 8456–8464. [Google Scholar] [CrossRef] [Green Version]
- Lorvik, K.B.; Hammarstrom, C.; Fauskanger, M.; Haabeth, O.A.; Zangani, M.; Haraldsen, G.; Bogen, B.; Corthay, A. Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering an In Situ Inflammatory Immune Response. Cancer Res. 2016, 76, 6864–6876. [Google Scholar] [CrossRef] [Green Version]
- Campbell, J.P.; Merkel, A.R.; Masood-Campbell, S.K.; Elefteriou, F.; Sterling, J.A. Models of bone metastasis. J. Vis. Exp. 2012, e4260. [Google Scholar] [CrossRef]
- Wright, L.E.; Ottewell, P.D.; Rucci, N.; Peyruchaud, O.; Pagnotti, G.M.; Chiechi, A.; Buijs, J.T.; Sterling, J.A. Murine models of breast cancer bone metastasis. Bonekey Rep. 2016, 5, 804. [Google Scholar] [CrossRef] [Green Version]
- Overwijk, W.W.; Restifo, N.P. B16 as a mouse model for human melanoma. Curr. Protoc. Immunol. 2001. [Google Scholar] [CrossRef] [PubMed]
- Arguello, F.; Baggs, R.B.; Frantz, C.N. A murine model of experimental metastasis to bone and bone marrow. Cancer Res. 1988, 48, 6876–6881. [Google Scholar]
- Zhang, K.; Kim, S.; Cremasco, V.; Hirbe, A.C.; Collins, L.; Piwnica-Worms, D.; Novack, D.V.; Weilbaecher, K.; Faccio, R. CD8+ T cells regulate bone tumor burden independent of osteoclast resorption. Cancer Res. 2011, 71, 4799–4808. [Google Scholar] [CrossRef] [Green Version]
- Pulaski, B.A.; Ostrand-Rosenberg, S. Mouse 4T1 breast tumor model. Curr. Protoc. Immunol. 2001. [Google Scholar] [CrossRef]
- Monteiro, A.C.; Leal, A.C.; Goncalves-Silva, T.; Mercadante, A.C.; Kestelman, F.; Chaves, S.B.; Azevedo, R.B.; Monteiro, J.P.; Bonomo, A. T cells induce pre-metastatic osteolytic disease and help bone metastases establishment in a mouse model of metastatic breast cancer. PLoS ONE 2013, 8, e68171. [Google Scholar] [CrossRef] [Green Version]
- Kotake, S.; Udagawa, N.; Takahashi, N.; Matsuzaki, K.; Itoh, K.; Ishiyama, S.; Saito, S.; Inoue, K.; Kamatani, N.; Gillespie, M.T.; et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J. Clin. Investig. 1999, 103, 1345–1352. [Google Scholar] [CrossRef]
- Kim, K.-W.; Kim, H.-R.; Kim, B.-M.; Cho, M.-L.; Lee, S.-H. Th17 Cytokines Regulate Osteoclastogenesis in Rheumatoid Arthritis. Am. J. Pathol. 2015, 185, 3011–3024. [Google Scholar] [CrossRef] [Green Version]
- Van Bezooijen, R.L.; Papapoulos, S.E.; Lowik, C.W. Effect of interleukin-17 on nitric oxide production and osteoclastic bone resorption: Is there dependency on nuclear factor-kappaB and receptor activator of nuclear factor kappaB (RANK)/RANK ligand signaling? Bone 2001, 28, 378–386. [Google Scholar] [CrossRef]
- Colucci, S.; Brunetti, G.; Rizzi, R.; Zonno, A.; Mori, G.; Colaianni, G.; Del Prete, D.; Faccio, R.; Liso, A.; Capalbo, S.; et al. T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: The role of the OPG/TRAIL interaction. Blood 2004, 104, 3722–3730. [Google Scholar] [CrossRef]
- Roato, I.; Grano, M.; Brunetti, G.; Colucci, S.; Mussa, A.; Bertetto, O.; Ferracini, R. Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. Faseb J. 2005, 19, 228–230. [Google Scholar] [CrossRef]
- Galon, J.; Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug. Discov. 2019, 18, 197–218. [Google Scholar] [CrossRef]
- Galon, J.; Pages, F.; Marincola, F.M.; Angell, H.K.; Thurin, M.; Lugli, A.; Zlobec, I.; Berger, A.; Bifulco, C.; Botti, G.; et al. Cancer classification using the Immunoscore: A worldwide task force. J. Transl. Med. 2012, 10, 205. [Google Scholar] [CrossRef]
- Kieper, W.C.; Tan, J.T.; Bondi-Boyd, B.; Gapin, L.; Sprent, J.; Ceredig, R.; Surh, C.D. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J. Exp. Med. 2002, 195, 1533–1539. [Google Scholar] [CrossRef]
- Li, J.; Huston, G.; Swain, S.L. IL-7 promotes the transition of CD4 effectors to persistent memory cells. J. Exp. Med. 2003, 198, 1807–1815. [Google Scholar] [CrossRef]
- Al-Rawi, M.A.; Rmali, K.; Watkins, G.; Mansel, R.E.; Jiang, W.G. Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer. Eur. J. Cancer 2004, 40, 494–502. [Google Scholar] [CrossRef]
- Giuliani, N.; Colla, S.; Sala, R.; Moroni, M.; Lazzaretti, M.; La Monica, S.; Bonomini, S.; Hojden, M.; Sammarelli, G.; Barille, S.; et al. Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: A potential role in multiple myeloma bone disease. Blood 2002, 100, 4615–4621. [Google Scholar] [CrossRef] [Green Version]
- Roato, I.; Brunetti, G.; Gorassini, E.; Grano, M.; Colucci, S.; Bonello, L.; Buffoni, L.; Manfredi, R.; Ruffini, E.; Ottaviani, D.; et al. IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor. PLoS ONE 2006, 1, e124. [Google Scholar] [CrossRef]
- Di Nicola, M.; Carlo-Stella, C.; Magni, M.; Milanesi, M.; Longoni, P.D.; Matteucci, P.; Grisanti, S.; Gianni, A.M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002, 99, 3838–3843. [Google Scholar] [CrossRef]
- Glennie, S.; Soeiro, I.; Dyson, P.J.; Lam, E.W.; Dazzi, F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005, 105, 2821–2827. [Google Scholar] [CrossRef]
- Plumas, J.; Chaperot, L.; Richard, M.J.; Molens, J.P.; Bensa, J.C.; Favrot, M.C. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 2005, 19, 1597–1604. [Google Scholar] [CrossRef]
- Batlle, E.; Massague, J. Transforming Growth Factor-beta Signaling in Immunity and Cancer. Immunity 2019, 50, 924–940. [Google Scholar] [CrossRef]
- Marie, J.C.; Liggitt, D.; Rudensky, A.Y. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 2006, 25, 441–454. [Google Scholar] [CrossRef] [Green Version]
- Curiel, T.J.; Coukos, G.; Zou, L.; Alvarez, X.; Cheng, P.; Mottram, P.; Evdemon-Hogan, M.; Conejo-Garcia, J.R.; Zhang, L.; Burow, M.; et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 2004, 10, 942–949. [Google Scholar] [CrossRef]
- Zou, L.; Barnett, B.; Safah, H.; Larussa, V.F.; Evdemon-Hogan, M.; Mottram, P.; Wei, S.; David, O.; Curiel, T.J.; Zou, W. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004, 64, 8451–8455. [Google Scholar] [CrossRef] [Green Version]
- Zhao, E.; Wang, L.; Dai, J.; Kryczek, I.; Wei, S.; Vatan, L.; Altuwaijri, S.; Sparwasser, T.; Wang, G.; Keller, E.T.; et al. Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Oncoimmunology 2012, 1, 152–161. [Google Scholar] [CrossRef] [Green Version]
- Zaiss, M.M.; Sarter, K.; Hess, A.; Engelke, K.; Bohm, C.; Nimmerjahn, F.; Voll, R.; Schett, G.; David, J.P. Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiation. Arthritis. Rheum. 2010, 62, 2328–2338. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.E.; Cook, R.J.; Major, P.; Lipton, A.; Saad, F.; Smith, M.; Lee, K.A.; Zheng, M.; Hei, Y.J.; Coleman, R.E. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J. Natl. Cancer Inst. 2005, 97, 59–69. [Google Scholar] [CrossRef] [Green Version]
- Ferreira, A.; Alho, I.; Casimiro, S.; Costa, L. Bone remodeling markers and bone metastases: From cancer research to clinical implications. Bonekey Rep. 2015, 4, 668. [Google Scholar] [CrossRef] [Green Version]
- Saad, F.; Eastham, J.A.; Smith, M.R. Biochemical markers of bone turnover and clinical outcomes in men with prostate cancer. Urol. Oncol. 2012, 30, 369–378. [Google Scholar] [CrossRef] [Green Version]
- Korpal, M.; Yan, J.; Lu, X.; Xu, S.; Lerit, D.A.; Kang, Y. Imaging transforming growth factor-β signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat. Med. 2009, 15, 960–966. [Google Scholar] [CrossRef]
- Edwards, J.R.; Nyman, J.S.; Lwin, S.T.; Moore, M.M.; Esparza, J.; O’Quinn, E.C.; Hart, A.J.; Biswas, S.; Patil, C.a.; Lonning, S.; et al. Inhibition of TGF-β signaling by 1D11 antibody treatment increases bone mass and quality in vivo. J. Bone Miner. Res. 2010, 25, 2419–2426. [Google Scholar] [CrossRef]
- Waning, D.L.; Mohammad, K.S.; Reiken, S.; Xie, W.; Andersson, D.C.; John, S.; Chiechi, A.; Wright, L.E.; Umanskaya, A.; Niewolna, M.; et al. Excess TGF-beta mediates muscle weakness associated with bone metastases in mice. Nat. Med. 2015, 21, 1262–1271. [Google Scholar] [CrossRef] [PubMed]
- Hu, Z.; Gupta, J.; Zhang, Z.; Gerseny, H.; Berg, A.; Chen, Y.J.; Du, H.; Brendler, C.; Xiao, X.; Pienta, K.; et al. Systemic delivery of oncolytic adenoviruses targeting transforming growth factor-beta inhibits established bone metastasis in a prostate cancer mouse model. Hum. Gene. Ther. 2012, 23, 871–882. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mohammad, K.; Javelaud, D.; Fournier, P.; Niewolna, M.; McKenna, C.; Peng, X.; Duong, V.; Dunn, L.; Mauviel, A.; Guise, T. TGF-β-RI Kinase Inhibitor SD-208 Reduces the Development and Progression of Melanoma Bone Metastases. Cancer Res. 2011, 71, 175–184. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, Y.; Xu, W.; Peng, D.; Wang, H.; Zhang, X.; Wang, H.; Xiao, F.; Zhu, Y.; Ji, Y.; Gulukota, K.; et al. An Oncolytic Adenovirus Targeting Transforming Growth Factor beta Inhibits Protumorigenic Signals and Produces Immune Activation: A Novel Approach to Enhance Anti-PD-1 and Anti-CTLA-4 Therapy. Hum. Gene. Ther. 2019, 30, 1117–1132. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Yang, Y.; Zhou, Q.; Weiss, J.M.; Howard, O.Z.; McPherson, J.M.; Wakefield, L.M.; Oppenheim, J.J. Effective chemoimmunotherapy with anti-TGFbeta antibody and cyclophosphamide in a mouse model of breast cancer. PLoS ONE 2014, 9, e85398. [Google Scholar] [CrossRef]
- Biswas, S.; Nyman, J.; Alvarez, J.; Chakrabarti, A.; Ayres, A.; Sterling, J.; Edwards, J.; Rana, T.; Johnson, R.; Perrien, D.; et al. Anti-transforming growth factor-b antibody treatment rescues bone loss and prevents breast cancer metastasis to bone. PLoS ONE 2011, 6, e27090. [Google Scholar] [CrossRef]
- Veglia, F.; Perego, M.; Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 2018, 19, 108–119. [Google Scholar] [CrossRef]
- Diaz-Montero, C.M.; Salem, M.L.; Nishimura, M.I.; Garrett-Mayer, E.; Cole, D.J.; Montero, A.J. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother. 2009, 58, 49–59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gonda, K.; Shibata, M.; Ohtake, T.; Matsumoto, Y.; Tachibana, K.; Abe, N.; Ohto, H.; Sakurai, K.; Takenoshita, S. Myeloid-derived suppressor cells are increased and correlated with type 2 immune responses, malnutrition, inflammation, and poor prognosis in patients with breast cancer. Oncol. Lett. 2017, 14, 1766–1774. [Google Scholar] [CrossRef] [Green Version]
- Chi, N.; Tan, Z.; Ma, K.; Bao, L.; Yun, Z. Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer. Int. J. Clin. Exp. Med. 2014, 7, 3181–3192. [Google Scholar]
- Idorn, M.; Kollgaard, T.; Kongsted, P.; Sengelov, L.; Thor Straten, P. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer. Cancer Immunol. Immunother. 2014, 63, 1177–1187. [Google Scholar] [CrossRef] [PubMed]
- Marvel, D.; Gabrilovich, D.I. Myeloid-derived suppressor cells in the tumor microenvironment: Expect the unexpected. J. Clin. Investig. 2015, 125, 3356–3364. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez, P.C.; Quiceno, D.G.; Zabaleta, J.; Ortiz, B.; Zea, A.H.; Piazuelo, M.B.; Delgado, A.; Correa, P.; Brayer, J.; Sotomayor, E.M.; et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 2004, 64, 5839–5849. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Srivastava, M.K.; Sinha, P.; Clements, V.K.; Rodriguez, P.; Ostrand-Rosenberg, S. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 2010, 70, 68–77. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sawant, A.; Deshane, J.; Jules, J.; Lee, C.M.; Harris, B.a.; Feng, X.; Ponnazhagan, S. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res. 2013, 73, 672–682. [Google Scholar] [CrossRef] [Green Version]
- Danilin, S.; Merkel, A.R.; Johnson, J.R.; Johnson, R.W.; Edwards, J.R.; Sterling, J.A. Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction. Oncoimmunology 2012, 1, 1484–1494. [Google Scholar] [CrossRef] [Green Version]
- Zhuang, J.; Zhang, J.; Lwin, S.T.; Edwards, J.R.; Edwards, C.M.; Mundy, G.R.; Yang, X. Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells. PLoS ONE 2012, 7, e48871. [Google Scholar] [CrossRef] [Green Version]
- Serafini, P.; Meckel, K.; Kelso, M.; Noonan, K.; Califano, J.; Koch, W.; Dolcetti, L.; Bronte, V.; Borrello, I. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J. Exp. Med. 2006, 203, 2691–2702. [Google Scholar] [CrossRef]
- Califano, J.A.; Khan, Z.; Noonan, K.A.; Rudraraju, L.; Zhang, Z.; Wang, H.; Goodman, S.; Gourin, C.G.; Ha, P.K.; Fakhry, C.; et al. Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. Clin. Cancer Res. 2015, 21, 30–38. [Google Scholar] [CrossRef] [Green Version]
- Tavazoie, M.F.; Pollack, I.; Tanqueco, R.; Ostendorf, B.N.; Reis, B.S.; Gonsalves, F.C.; Kurth, I.; Andreu-Agullo, C.; Derbyshire, M.L.; Posada, J.; et al. LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer. Cell 2018, 172, 825–840.e818. [Google Scholar] [CrossRef]
- Jiang, K.; Li, J.; Zhang, J.; Wang, L.; Zhang, Q.; Ge, J.; Guo, Y.; Wang, B.; Huang, Y.; Yang, T.; et al. SDF-1/CXCR4 axis facilitates myeloid-derived suppressor cells accumulation in osteosarcoma microenvironment and blunts the response to anti-PD-1 therapy. Int. Immunopharmacol. 2019, 75, 105818. [Google Scholar] [CrossRef]
- Zhang, J.; Pang, Y.; Xie, T.; Zhu, L. CXCR4 antagonism in combination with IDO1 inhibition weakens immune suppression and inhibits tumor growth in mouse breast cancer bone metastases. Onco. Targets Ther. 2019, 12, 4985–4992. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Melani, C.; Sangaletti, S.; Barazzetta, F.M.; Werb, Z.; Colombo, M.P. Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res. 2007, 67, 11438–11446. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Corzo, C.A.; Condamine, T.; Lu, L.; Cotter, M.J.; Youn, J.I.; Cheng, P.; Cho, H.I.; Celis, E.; Quiceno, D.G.; Padhya, T.; et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 2010, 207, 2439–2453. [Google Scholar] [CrossRef] [PubMed]
- Dunn, L.; Mohammad, K.; Fournier, P.; McKenna, C.; Davis, H.; Niewolna, M.; Peng, X.; Chirgwin, J.; Guise, T. Hypoxia and TGF-b drive breast cancer bone metastases through parallel signaling pathways in tumor cells and the bone microenvironment. PLoS ONE 2009, 4, e6896. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hirao, M.; Hashimoto, J.; Yamasaki, N.; Ando, W.; Tsuboi, H.; Myoui, A.; Yoshikawa, H. Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes. J. Bone Miner. Metab. 2007, 25, 266–276. [Google Scholar] [CrossRef]
- Kumar, V.; Gabrilovich, D.I. Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment. Immunology 2014, 143, 512–519. [Google Scholar] [CrossRef] [Green Version]
- Multhoff, G.; Vaupel, P. Hypoxia Compromises Anti-Cancer Immune Responses. Adv. Exp. Med. Biol. 2020, 1232, 131–143. [Google Scholar] [CrossRef]
- Chang, C.H.; Qiu, J.; O’Sullivan, D.; Buck, M.D.; Noguchi, T.; Curtis, J.D.; Chen, Q.; Gindin, M.; Gubin, M.M.; van der Windt, G.J.; et al. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell 2015, 162, 1229–1241. [Google Scholar] [CrossRef] [Green Version]
- Cham, C.M.; Driessens, G.; O’Keefe, J.P.; Gajewski, T.F. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. Eur. J. Immunol. 2008, 38, 2438–2450. [Google Scholar] [CrossRef] [Green Version]
- Chouaib, S.; Noman, M.Z.; Kosmatopoulos, K.; Curran, M.A. Hypoxic stress: Obstacles and opportunities for innovative immunotherapy of cancer. Oncogene 2017, 36, 439–445. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brand, A.; Singer, K.; Koehl, G.E.; Kolitzus, M.; Schoenhammer, G.; Thiel, A.; Matos, C.; Bruss, C.; Klobuch, S.; Peter, K.; et al. LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab. 2016, 24, 657–671. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fischer, K.; Hoffmann, P.; Voelkl, S.; Meidenbauer, N.; Ammer, J.; Edinger, M.; Gottfried, E.; Schwarz, S.; Rothe, G.; Hoves, S.; et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 2007, 109, 3812–3819. [Google Scholar] [CrossRef] [PubMed]
- Mendler, A.N.; Hu, B.; Prinz, P.U.; Kreutz, M.; Gottfried, E.; Noessner, E. Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun activation. Int. J. Cancer 2012, 131, 633–640. [Google Scholar] [CrossRef] [PubMed]
- Siemens, D.R.; Hu, N.; Sheikhi, A.K.; Chung, E.; Frederiksen, L.J.; Pross, H.; Graham, C.H. Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: Role of nitric oxide. Cancer Res. 2008, 68, 4746–4753. [Google Scholar] [CrossRef] [Green Version]
- Groh, V.; Wu, J.; Yee, C.; Spies, T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002, 419, 734–738. [Google Scholar] [CrossRef]
- Blank, C.U.; Haanen, J.B.; Ribas, A.; Schumacher, T.N. Cancer Immunology: The “cancer immunogram”. Science 2016, 352, 658–660. [Google Scholar] [CrossRef]
- Adami, S.; Bhalla, A.K.; Dorizzi, R.; Montesanti, F.; Rosini, S.; Salvagno, G.; Lo Cascio, V. The acute-phase response after bisphosphonate administration. Calcif. Tissue. Int. 1987, 41, 326–331. [Google Scholar] [CrossRef]
- Hewitt, R.E.; Lissina, A.; Green, A.E.; Slay, E.S.; Price, D.A.; Sewell, A.K. The bisphosphonate acute phase response: Rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin. Exp. Immunol. 2005, 139, 101–111. [Google Scholar] [CrossRef]
- Gober, H.J.; Kistowska, M.; Angman, L.; Jeno, P.; Mori, L.; De Libero, G. Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. J. Exp. Med. 2003, 197, 163–168. [Google Scholar] [CrossRef]
- Wang, H.; Sarikonda, G.; Puan, K.J.; Tanaka, Y.; Feng, J.; Giner, J.L.; Cao, R.; Monkkonen, J.; Oldfield, E.; Morita, C.T. Indirect stimulation of human Vgamma2Vdelta2 T cells through alterations in isoprenoid metabolism. J. Immunol. 2011, 187, 5099–5113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Benzaid, I.; Monkkonen, H.; Bonnelye, E.; Monkkonen, J.; Clezardin, P. In vivo phosphoantigen levels in bisphosphonate-treated human breast tumors trigger Vgamma9Vdelta2 T-cell antitumor cytotoxicity through ICAM-1 engagement. Clin. Cancer Res. 2012, 18, 6249–6259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morita, C.T.; Jin, C.; Sarikonda, G.; Wang, H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: Discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol. Rev. 2007, 215, 59–76. [Google Scholar] [CrossRef] [PubMed]
- Zysk, A.; DeNichilo, M.O.; Panagopoulos, V.; Zinonos, I.; Liapis, V.; Hay, S.; Ingman, W.; Ponomarev, V.; Atkins, G.; Findlay, D.; et al. Adoptive transfer of ex vivo expanded Vgamma9Vdelta2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer. Cancer Lett. 2017, 386, 141–150. [Google Scholar] [CrossRef] [Green Version]
- Ma, C.; Zhang, Q.; Ye, J.; Wang, F.; Zhang, Y.; Wevers, E.; Schwartz, T.; Hunborg, P.; Varvares, M.A.; Hoft, D.F.; et al. Tumor-infiltrating gammadelta T lymphocytes predict clinical outcome in human breast cancer. J. Immunol. 2012, 189, 5029–5036. [Google Scholar] [CrossRef] [Green Version]
- Kobayashi, H.; Tanaka, Y.; Yagi, J.; Minato, N.; Tanabe, K. Phase I/II study of adoptive transfer of gammadelta T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma. Cancer Immunol. Immunother. 2011, 60, 1075–1084. [Google Scholar] [CrossRef]
- Nicol, A.J.; Tokuyama, H.; Mattarollo, S.R.; Hagi, T.; Suzuki, K.; Yokokawa, K.; Nieda, M. Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours. Br. J. Cancer 2011, 105, 778–786. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, Y.; Murata-Hirai, K.; Iwasaki, M.; Matsumoto, K.; Hayashi, K.; Kumagai, A.; Nada, M.H.; Wang, H.; Kobayashi, H.; Kamitakahara, H.; et al. Expansion of human gammadelta T cells for adoptive immunotherapy using a bisphosphonate prodrug. Cancer Sci. 2018, 109, 587–599. [Google Scholar] [CrossRef] [Green Version]
- Zhou, X.; Gu, Y.; Xiao, H.; Kang, N.; Xie, Y.; Zhang, G.; Shi, Y.; Hu, X.; Oldfield, E.; Zhang, X.; et al. Combining Vgamma9Vdelta2 T Cells with a Lipophilic Bisphosphonate Efficiently Kills Activated Hepatic Stellate Cells. Front. Immunol. 2017, 8, 1381. [Google Scholar] [CrossRef] [Green Version]
- 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]
- Gros, A.; Parkhurst, M.R.; Tran, E.; Pasetto, A.; Robbins, P.F.; Ilyas, S.; Prickett, T.D.; Gartner, J.J.; Crystal, J.S.; Roberts, I.M.; et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat. Med. 2016, 22, 433–438. [Google Scholar] [CrossRef] [PubMed]
- Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Rutkowski, P.; Lao, C.D.; Cowey, C.L.; Schadendorf, D.; Wagstaff, J.; Dummer, R.; et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 2019, 381, 1535–1546. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hellmann, M.D.; Ciuleanu, T.E.; Pluzanski, A.; Lee, J.S.; Otterson, G.A.; Audigier-Valette, C.; Minenza, E.; Linardou, H.; Burgers, S.; Salman, P.; et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N. Engl. J. Med. 2018, 378, 2093–2104. [Google Scholar] [CrossRef] [PubMed]
- Postow, M.A.; Sidlow, R.; Hellmann, M.D. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N. Engl. J. Med. 2018, 378, 158–168. [Google Scholar] [CrossRef] [PubMed]
- Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [Green Version]
- Samstein, R.M.; Lee, C.H.; Shoushtari, A.N.; Hellmann, M.D.; Shen, R.; Janjigian, Y.Y.; Barron, D.A.; Zehir, A.; Jordan, E.J.; Omuro, A.; et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 2019, 51, 202–206. [Google Scholar] [CrossRef]
- Alexandrov, L.B.; Kim, J.; Haradhvala, N.J.; Huang, M.N.; Tian Ng, A.W.; Wu, Y.; Boot, A.; Covington, K.R.; Gordenin, D.A.; Bergstrom, E.N.; et al. The repertoire of mutational signatures in human cancer. Nature 2020, 578, 94–101. [Google Scholar] [CrossRef] [Green Version]
- Coleman, R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin. Cancer Res. 2006, 12, 6243s–6249s. [Google Scholar] [CrossRef] [Green Version]
- Grover, P.; Karivedu, V.; Zhu, Z.; Jandarov, R.; Wise-Draper, T.M. Bone metastases treated with immune checkpoint inhibitors: A single center experience. J. Clin. Oncol. 2019, 37, e14105. [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]
- 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. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 2018, 554, 538–543. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Verma, V.; Sprave, T.; Haque, W.; Simone, C.B., 2nd; Chang, J.Y.; Welsh, J.W.; Thomas, C.R., Jr. A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors. J. Immunother. Cancer 2018, 6, 128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sedykh, S.E.; Prinz, V.V.; Buneva, V.N.; Nevinsky, G.A. Bispecific antibodies: Design, therapy, perspectives. Drug. Des. Devel. Ther. 2018, 12, 195–208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ravi, R.; Noonan, K.A.; Pham, V.; Bedi, R.; Zhavoronkov, A.; Ozerov, I.V.; Makarev, E.; A, V.A.; Wysocki, P.T.; Mehra, R.; et al. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat. Commun. 2018, 9, 741. [Google Scholar] [CrossRef] [PubMed]
- Hummel, H.-D.; Kufer, P.; Grüllich, C.; Deschler-Baier, B.; Chatterjee, M.; Goebeler, M.-E.; Miller, K.; De Santis, M.; Loidl, W.C.; Buck, A.; et al. Phase 1 study of pasotuxizumab (BAY 2010112), a PSMA-targeting Bispecific T cell Engager (BiTE) immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 2019, 37, e5034. [Google Scholar] [CrossRef]
- Wu, L.; Seung, E.; Xu, L.; Rao, E.; Lord, D.M.; Wei, R.R.; Cortez-Retamozo, V.; Ospina, B.; Posternak, V.; Ulinski, G.; et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nature Cancer 2020, 1, 86–98. [Google Scholar] [CrossRef]
- Yang, J.C.; Rosenberg, S.A. Adoptive T-Cell Therapy for Cancer. Adv. Immunol. 2016, 130, 279–294. [Google Scholar] [CrossRef]
- Rosenberg, S.A.; Yang, J.C.; Sherry, R.M.; Kammula, U.S.; Hughes, M.S.; Phan, G.Q.; Citrin, D.E.; Restifo, N.P.; Robbins, P.F.; Wunderlich, J.R.; et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 2011, 17, 4550–4557. [Google Scholar] [CrossRef] [Green Version]
- Zacharakis, N.; Chinnasamy, H.; Black, M.; Xu, H.; Lu, Y.C.; Zheng, Z.; Pasetto, A.; Langhan, M.; Shelton, T.; Prickett, T.; et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat. Med. 2018, 24, 724–730. [Google Scholar] [CrossRef]
- Garfall, A.L.; Stadtmauer, E.A.; Hwang, W.T.; Lacey, S.F.; Melenhorst, J.J.; Krevvata, M.; Carroll, M.P.; Matsui, W.H.; Wang, Q.; Dhodapkar, M.V.; et al. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight 2018, 3. [Google Scholar] [CrossRef]
- Lin, Q.; Zhao, J.; Song, Y.; Liu, D. Recent updates on CAR T clinical trials for multiple myeloma. Mol. Cancer 2019, 18, 154. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cohen, A.D.; Garfall, A.L.; Stadtmauer, E.A.; Melenhorst, J.J.; Lacey, S.F.; Lancaster, E.; Vogl, D.T.; Weiss, B.M.; Dengel, K.; Nelson, A.; et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J. Clin. Investig. 2019, 129, 2210–2221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Radhakrishnan, S.V.; Luetkens, T.; Scherer, S.D.; Davis, P.; Vander Mause, E.R.; Olson, M.L.; Yousef, S.; Panse, J.; Abdiche, Y.; Li, K.D.; et al. CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Nat. Commun. 2020, 11, 798. [Google Scholar] [CrossRef] [PubMed]
- Schepisi, G.; Cursano, M.C.; Casadei, C.; Menna, C.; Altavilla, A.; Lolli, C.; Cerchione, C.; Paganelli, G.; Santini, D.; Tonini, G.; et al. CAR-T cell therapy: A potential new strategy against prostate cancer. J. Immunother. Cancer 2019, 7, 258. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Zhou, P. New Approaches in CAR-T Cell Immunotherapy for Breast Cancer. Adv. Exp. Med. Biol. 2017, 1026, 371–381. [Google Scholar] [CrossRef]
- Wu, C.Y.; Roybal, K.T.; Puchner, E.M.; Onuffer, J.; Lim, W.A. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 2015, 350, aab4077. [Google Scholar] [CrossRef] [Green Version]
- Stadtmauer, E.A.; Fraietta, J.A.; Davis, M.M.; Cohen, A.D.; Weber, K.L.; Lancaster, E.; Mangan, P.A.; Kulikovskaya, I.; Gupta, M.; Chen, F.; et al. CRISPR-engineered T cells in patients with refractory cancer. Science 2020, 367. [Google Scholar] [CrossRef]
© 2020 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
Mendoza-Reinoso, V.; McCauley, L.K.; Fournier, P.G.J. Contribution of Macrophages and T Cells in Skeletal Metastasis. Cancers 2020, 12, 1014. https://doi.org/10.3390/cancers12041014
Mendoza-Reinoso V, McCauley LK, Fournier PGJ. Contribution of Macrophages and T Cells in Skeletal Metastasis. Cancers. 2020; 12(4):1014. https://doi.org/10.3390/cancers12041014
Chicago/Turabian StyleMendoza-Reinoso, Veronica, Laurie K. McCauley, and Pierrick G.J. Fournier. 2020. "Contribution of Macrophages and T Cells in Skeletal Metastasis" Cancers 12, no. 4: 1014. https://doi.org/10.3390/cancers12041014