Novel Biomarkers for Personalized Cancer Immunotherapy
Abstract
:1. Introduction
2. Biomarkers in Tumors and the Tumor Microenvironment
2.1. PD-L1
2.2. Tumor Mutational Burden, Mismatch Repair Deficiency, and Neoantigens
2.3. Tumor-Infiltrating Lymphocytes (TILs)
2.4. Tumor-Infiltrating Tregs and Myeloid Cells
3. Biomarkers in Peripheral Blood
3.1. Lymphocytes and Neutrophils
3.2. Lactate Dehydrogenase (LDH)
3.3. C-Reactive Protein (CRP)
3.4. MicroRNA (miRNA)
3.5. Circulating Tregs and MDSCs
3.6. Ki-67 Expression in PD-1+ CD8+ T Cells
4. Biomarkers in Other Sources
Microbiome
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Yoshino, S.; Nishikawa, K.; Morita, S.; Takahashi, T.; Sakata, K.; Nagao, J.; Nemoto, H.; Murakami, N.; Matsuda, T.; Hasegawa, H.; et al. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur. J. Cancer 2016, 65, 164–171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rayner, A.A.; Grimm, E.A.; Lotze, M.T.; Chu, E.W.; Rosenberg, S.A. Lymphokine-activated killer (LAK) cells. Analysis of factors relevant to the immunotherapy of human cancer. Cancer 1985, 55, 1327–1333. [Google Scholar] [CrossRef]
- Turcotte, S.; Gros, A.; Tran, E.; Lee, C.C.; Wunderlich, J.R.; Robbins, P.F.; Rosenberg, S.A. Tumor-reactive CD8+ T cells in metastatic gastrointestinal cancer refractory to chemotherapy. Clin. Cancer Res. 2014, 20, 331–343. [Google Scholar] [CrossRef]
- Matsui, H.; Hazama, S.; Sakamoto, K.; Shindo, Y.; Kanekiyo, S.; Nakashima, M.; Matsukuma, S.; Tokuhisa, Y.; Iida, M.; Suzuki, N.; et al. Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy. Pancreas 2017, 46, 994–1002. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maeda, Y.; Yoshimura, K.; Matsui, H.; Shindo, Y.; Tamesa, T.; Tokumitsu, Y.; Hashimoto, N.; Tokuhisa, Y.; Sakamoto, K.; Sakai, K.; et al. Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma: A phase 1 dose escalation clinical trial. Cancer Immunol. Immunother. CII 2015, 64, 1047–1056. [Google Scholar] [CrossRef] [PubMed]
- Shindo, Y.; Hazama, S.; Maeda, Y.; Matsui, H.; Iida, M.; Suzuki, N.; Yoshimura, K.; Ueno, T.; Yoshino, S.; Sakai, K.; et al. Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer. J. Transl. Med. 2014, 12, 175. [Google Scholar] [CrossRef]
- Hazama, S.; Nakamura, Y.; Tanaka, H.; Hirakawa, K.; Tahara, K.; Shimizu, R.; Ozasa, H.; Etoh, R.; Sugiura, F.; Okuno, K.; et al. A phase IotaI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). J. Transl. Med. 2014, 12, 108. [Google Scholar] [CrossRef]
- Suzuki, N.; Hazama, S.; Iguchi, H.; Uesugi, K.; Tanaka, H.; Hirakawa, K.; Aruga, A.; Hatori, T.; Ishizaki, H.; Umeda, Y.; et al. Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study. Cancer Sci. 2017, 108, 73–80. [Google Scholar] [CrossRef] [PubMed]
- Handy, C.E.; Antonarakis, E.S. Sipuleucel-T for the treatment of prostate cancer: Novel insights and future directions. Future Oncol. 2018, 14, 907–917. [Google Scholar] [CrossRef] [PubMed]
- Kano, Y.; Iguchi, T.; Matsui, H.; Adachi, K.; Sakoda, Y.; Miyakawa, T.; Doi, S.; Hazama, S.; Nagano, H.; Ueyama, Y.; et al. Combined adjuvants of poly(I:C) plus LAG-3-Ig improve antitumor effects of tumor-specific T cells, preventing their exhaustion. Cancer Sci. 2016, 107, 398–406. [Google Scholar] [CrossRef]
- Hazama, S.; Tamada, K.; Yamaguchi, Y.; Kawakami, Y.; Nagano, H. Current status of immunotherapy against gastrointestinal cancers and its biomarkers: Perspective for precision immunotherapy. Ann. Gastroenterol. Surg. 2018, 2, 289–303. [Google Scholar] [CrossRef]
- Sheikh, N.A.; Petrylak, D.; Kantoff, P.W.; Dela Rosa, C.; Stewart, F.P.; Kuan, L.Y.; Whitmore, J.B.; Trager, J.B.; Poehlein, C.H.; Frohlich, M.W.; et al. Sipuleucel-T immune parameters correlate with survival: An analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol. Immunother. CII 2013, 62, 137–147. [Google Scholar] [CrossRef] [PubMed]
- Torphy, R.J.; Zhu, Y.; Schulick, R.D. Immunotherapy for pancreatic cancer: Barriers and breakthroughs. Ann. Gastroenterol. Surg. 2018, 2, 274–281. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kono, K. Advances in cancer immunotherapy for gastroenterological malignancy. Ann. Gastroenterol. Surg. 2018, 2, 244–245. [Google Scholar] [CrossRef]
- Hodi, F.S.; O’Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C.; et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363, 711–723. [Google Scholar] [CrossRef]
- Topalian, S.L.; Hodi, F.S.; Brahmer, J.R.; Gettinger, S.N.; Smith, D.C.; McDermott, D.F.; Powderly, J.D.; Carvajal, R.D.; Sosman, J.A.; Atkins, M.B.; et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012, 366, 2443–2454. [Google Scholar] [CrossRef] [PubMed]
- Shindo, Y.; Yoshimura, K.; Kuramasu, A.; Watanabe, Y.; Ito, H.; Kondo, T.; Oga, A.; Ito, H.; Yoshino, S.; Hazama, S.; et al. Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. Anticancer Res. 2015, 35, 129–136. [Google Scholar] [PubMed]
- Wei, S.C.; Duffy, C.R.; Allison, J.P. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018, 8, 1069–1086. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brahmer, J.; Reckamp, K.L.; Baas, P.; Crino, L.; Eberhardt, W.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 123–135. [Google Scholar] [CrossRef] [PubMed]
- Postow, M.A.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.; McDermott, D.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 2015, 372, 2006–2017. [Google Scholar] [CrossRef]
- Garon, E.B.; Rizvi, N.A.; Hui, R.; Leighl, N.; Balmanoukian, A.S.; Eder, J.P.; Patnaik, A.; Aggarwal, C.; Gubens, M.; Horn, L.; et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 2015, 372, 2018–2028. [Google Scholar] [CrossRef]
- Herbst, R.S.; Baas, P.; Kim, D.W.; Felip, E.; Perez-Gracia, J.L.; Han, J.Y.; Molina, J.; Kim, J.H.; Arvis, C.D.; Ahn, M.J.; et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016, 387, 1540–1550. [Google Scholar] [CrossRef]
- Reck, M.; Rodriguez-Abreu, D.; Robinson, A.G.; Hui, R.; Csoszi, T.; Fulop, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2016, 375, 1823–1833. [Google Scholar] [CrossRef]
- Balar, A.V.; Castellano, D.; O’Donnell, P.H.; Grivas, P.; Vuky, J.; Powles, T.; Plimack, E.R.; Hahn, N.M.; de Wit, R.; Pang, L.; et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): A multicentre, single-arm, phase 2 study. Lancet. Oncol. 2017, 18, 1483–1492. [Google Scholar] [CrossRef]
- Apolo, A.B.; Infante, J.R.; Balmanoukian, A.; Patel, M.R.; Wang, D.; Kelly, K.; Mega, A.E.; Britten, C.D.; Ravaud, A.; Mita, A.C.; et al. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J. Clin. Oncol. 2017, 35, 2117–2124. [Google Scholar] [CrossRef] [PubMed]
- Snyder, A.; Makarov, V.; Merghoub, T.; Yuan, J.; Zaretsky, J.M.; Desrichard, A.; Walsh, L.A.; Postow, M.A.; Wong, P.; Ho, T.S.; et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 2014, 371, 2189–2199. [Google Scholar] [CrossRef]
- Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M.M.; Ciuleanu, T.E.; Badin, F.; et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 376, 2415–2426. [Google Scholar] [CrossRef] [PubMed]
- Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N. Engl. J. Med. 2015, 372, 2509–2520. [Google Scholar] [CrossRef] [PubMed]
- Muro, K.; Chung, H.C.; Shankaran, V.; Geva, R.; Catenacci, D.; Gupta, S.; Eder, J.P.; Golan, T.; Le, D.T.; Burtness, B.; et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial. Lancet. Oncol. 2016, 17, 717–726. [Google Scholar] [CrossRef]
- Alley, E.W.; Lopez, J.; Santoro, A.; Morosky, A.; Saraf, S.; Piperdi, B.; van Brummelen, E. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): Preliminary results from a non-randomised, open-label, phase 1b trial. Lancet. Oncol. 2017, 18, 623–630. [Google Scholar] [CrossRef]
- Chung, H.C.; Ros, W.; Delord, J.P.; Perets, R.; Italiano, A.; Shapira-Frommer, R.; Manzuk, L.; Piha-Paul, S.A.; Xu, L.; Zeigenfuss, S.; et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J. Clin. Oncol. 2019, 37, 1470–1478. [Google Scholar] [CrossRef]
- Lemery, S.; Keegan, P.; Pazdur, R. First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication. N. Engl. J. Med. 2017, 377, 1409–1412. [Google Scholar] [CrossRef] [PubMed]
- Yan, L.; Zhang, W. Precision medicine becomes reality-tumor type-agnostic therapy. Cancer Commun. 2018, 38, 6. [Google Scholar] [CrossRef]
- Berghuis, D.; Santos, S.J.; Baelde, H.J.; Taminiau, A.H.; Egeler, R.M.; Schilham, M.W.; Hogendoorn, P.C.; Lankester, A.C. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression. J. Pathol. 2011, 223, 347–357. [Google Scholar] [CrossRef] [PubMed]
- Gerber, A.L.; Munst, A.; Schlapbach, C.; Shafighi, M.; Kiermeir, D.; Husler, R.; Hunger, R.E. High expression of FOXP3 in primary melanoma is associated with tumour progression. Br. J. Dermatol. 2014, 170, 103–109. [Google Scholar] [CrossRef] [PubMed]
- Galon, J.; Costes, A.; Sanchez-Cabo, F.; Kirilovsky, A.; Mlecnik, B.; Lagorce-Pages, C.; Tosolini, M.; Camus, M.; Berger, A.; Wind, P.; et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006, 313, 1960–1964. [Google Scholar] [CrossRef] [PubMed]
- Polcher, M.; Braun, M.; Friedrichs, N.; Rudlowski, C.; Bercht, E.; Fimmers, R.; Sauerwald, A.; Keyver-Paik, M.D.; Kubler, K.; Buttner, R.; et al. Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol. Immunother. CII 2010, 59, 909–919. [Google Scholar] [CrossRef]
- Zeng, D.Q.; Yu, Y.F.; Ou, Q.Y.; Li, X.Y.; Zhong, R.Z.; Xie, C.M.; Hu, Q.G. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget 2016, 7, 13765–13781. [Google Scholar] [CrossRef] [PubMed]
- Tumeh, P.C.; Harview, C.L.; Yearley, J.H.; Shintaku, I.P.; Taylor, E.J.; Robert, L.; Chmielowski, B.; Spasic, M.; Henry, G.; Ciobanu, V.; et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014, 515, 568–571. [Google Scholar] [CrossRef] [PubMed]
- Shang, B.; Liu, Y.; Jiang, S.J.; Liu, Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: A systematic review and meta-analysis. Sci. Rep. 2015, 5, 15179. [Google Scholar] [CrossRef] [PubMed]
- Liakou, C.I.; Kamat, A.; Tang, D.N.; Chen, H.; Sun, J.; Troncoso, P.; Logothetis, C.; Sharma, P. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl. Acad. Sci. USA 2008, 105, 14987–14992. [Google Scholar] [CrossRef] [PubMed]
- Shitara, K.; Nishikawa, H. Regulatory T cells: A potential target in cancer immunotherapy. Ann. N. Y. Acad. Sci. 2018, 1417, 104–115. [Google Scholar] [CrossRef]
- Bronte, V.; Zanovello, P. Regulation of immune responses by L-arginine metabolism. Nat. Rev. Immunol. 2005, 5, 641–654. [Google Scholar] [CrossRef] [PubMed]
- Gabrilovich, D.I.; Ostrand-Rosenberg, S.; Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 2012, 12, 253–268. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Platten, M.; Wick, W.; Van den Eynde, B.J. Tryptophan catabolism in cancer: Beyond IDO and tryptophan depletion. Cancer Res. 2012, 72, 5435–5440. [Google Scholar] [CrossRef] [PubMed]
- Meirow, Y.; Kanterman, J.; Baniyash, M. Paving the Road to Tumor Development and Spreading: Myeloid-Derived Suppressor Cells are Ruling the Fate. Front. Immunol. 2015, 6, 523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zahorec, R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy 2001, 102, 5–14. [Google Scholar] [PubMed]
- Shindo, Y.; Hazama, S.; Suzuki, N.; Iguchi, H.; Uesugi, K.; Tanaka, H.; Aruga, A.; Hatori, T.; Ishizaki, H.; Umeda, Y.; et al. Predictive biomarkers for the efficacy of peptide vaccine treatment: Based on the results of a phase II study on advanced pancreatic cancer. J. Exp. Clin. Cancer Res. CR 2017, 36, 36. [Google Scholar] [CrossRef] [PubMed]
- Maymani, H.; Hess, K.; Groisberg, R.; Hong, D.S.; Naing, A.; Piha-Paul, S.; Janku, F.; Fu, S.; Tsimberidou, A.M.; Pant, S.; et al. Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. Lung Cancer 2018, 120, 137–141. [Google Scholar] [CrossRef]
- Bilen, M.A.; Martini, D.J.; Liu, Y.; Lewis, C.; Collins, H.H.; Shabto, J.M.; Akce, M.; Kissick, H.T.; Carthon, B.C.; Shaib, W.L.; et al. The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy. Cancer 2019, 125, 127–134. [Google Scholar] [CrossRef] [PubMed]
- Kelderman, S.; Heemskerk, B.; van Tinteren, H.; van den Brom, R.R.; Hospers, G.A.; van den Eertwegh, A.J.; Kapiteijn, E.W.; de Groot, J.W.; Soetekouw, P.; Jansen, R.L.; et al. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol. Immunother. CII 2014, 63, 449–458. [Google Scholar] [CrossRef] [PubMed]
- Weide, B.; Martens, A.; Hassel, J.C.; Berking, C.; Postow, M.A.; Bisschop, K.; Simeone, E.; Mangana, J.; Schilling, B.; Di Giacomo, A.M.; et al. Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clin. Cancer Res. 2016, 22, 5487–5496. [Google Scholar] [CrossRef] [PubMed]
- Diem, S.; Kasenda, B.; Spain, L.; Martin-Liberal, J.; Marconcini, R.; Gore, M.; Larkin, J. Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br. J. Cancer 2016, 114, 256–261. [Google Scholar] [CrossRef] [PubMed]
- Wagner, N.B.; Forschner, A.; Leiter, U.; Garbe, C.; Eigentler, T.K. S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies. Br. J. Cancer 2018, 119, 339–346. [Google Scholar] [CrossRef] [PubMed]
- Deng, T.; Zhang, J.; Meng, Y.; Zhou, Y.; Li, W. Higher pretreatment lactate dehydrogenase concentration predicts worse overall survival in patients with lung cancer. Medicine 2018, 97, e12524. [Google Scholar] [CrossRef]
- Oya, Y.; Yoshida, T.; Kuroda, H.; Mikubo, M.; Kondo, C.; Shimizu, J.; Horio, Y.; Sakao, Y.; Hida, T.; Yatabe, Y. Predictive clinical parameters for the response of nivolumab in pretreated advanced non-small-cell lung cancer. Oncotarget 2017, 8, 103117–103128. [Google Scholar] [CrossRef] [PubMed]
- Inomata, M.; Hirai, T.; Seto, Z.; Tokui, K.; Taka, C.; Okazawa, S.; Kambara, K.; Ichikawa, T.; Imanishi, S.; Yamada, T.; et al. Clinical Parameters for Predicting the Survival in Patients with Squamous and Non-squamous-cell NSCLC Receiving PD-1 Inhibitor Therapy. Pathol. Oncol. Res. POR 2018. [Google Scholar] [CrossRef] [PubMed]
- Ichiki, Y.; Taira, A.; Chikaishi, Y.; Matsumiya, H.; Mori, M.; Kanayama, M.; Nabe, Y.; Shinohara, S.; Kuwata, T.; Takenaka, M.; et al. Prognostic factors of advanced or postoperative recurrent non-small cell lung cancer targeted with immune check point inhibitors. J. Thorac. Dis. 2019, 11, 1117–1123. [Google Scholar] [CrossRef]
- Wang, X.; Zhang, B.; Chen, X.; Mo, H.; Wu, D.; Lan, B.; Li, Q.; Xu, B.; Huang, J. Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR-1210), a novel anti-PD-1 antibody. Thorac. Cancer 2019, 10, 1395–1401. [Google Scholar] [CrossRef]
- Simeone, E.; Gentilcore, G.; Giannarelli, D.; Grimaldi, A.M.; Caraco, C.; Curvietto, M.; Esposito, A.; Paone, M.; Palla, M.; Cavalcanti, E.; et al. Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. Cancer Immunol. Immunother. CII 2014, 63, 675–683. [Google Scholar] [CrossRef] [PubMed]
- Kijima, T.; Hazama, S.; Tsunedomi, R.; Tanaka, H.; Takenouchi, H.; Kanekiyo, S.; Inoue, Y.; Nakashima, M.; Iida, M.; Sakamoto, K.; et al. MicroRNA-6826 and -6875 in plasma are valuable noninvasive biomarkers that predict the efficacy of vaccine treatment against metastatic colorectal cancer. Oncol. Rep. 2017, 37, 23–30. [Google Scholar] [CrossRef] [PubMed]
- Halvorsen, A.R.; Sandhu, V.; Sprauten, M.; Flote, V.G.; Kure, E.H.; Brustugun, O.T.; Helland, A. Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab. Acta Oncol. 2018, 57, 1225–1231. [Google Scholar] [CrossRef] [Green Version]
- Nakamura, Y. Biomarkers for Immune Checkpoint Inhibitor-Mediated Tumor Response and Adverse Events. Front. Med. 2019, 6, 119. [Google Scholar] [CrossRef] [Green Version]
- Kamphorst, A.O.; Pillai, R.N.; Yang, S.; Nasti, T.H.; Akondy, R.S.; Wieland, A.; Sica, G.L.; Yu, K.; Koenig, L.; Patel, N.T.; et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc. Natl. Acad. Sci. USA 2017, 114, 4993–4998. [Google Scholar] [CrossRef]
- Huang, A.C.; Postow, M.A.; Orlowski, R.J.; Mick, R.; Bengsch, B.; Manne, S.; Xu, W.; Harmon, S.; Giles, J.R.; Wenz, B.; et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 2017, 545, 60–65. [Google Scholar] [CrossRef] [Green Version]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef] [PubMed]
- Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.P.M.; Alou, M.T.; Daillere, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018, 359, 91–97. [Google Scholar] [CrossRef] [PubMed]
- Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 2015, 372, 320–330. [Google Scholar] [CrossRef]
- Motzer, R.J.; Rini, B.I.; McDermott, D.F.; Redman, B.G.; Kuzel, T.M.; Harrison, M.R.; Vaishampayan, U.N.; Drabkin, H.A.; George, S.; Logan, T.F.; et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J. Clin. Oncol. 2015, 33, 1430–1437. [Google Scholar] [CrossRef]
- Mansfield, A.S.; Aubry, M.C.; Moser, J.C.; Harrington, S.M.; Dronca, R.S.; Park, S.S.; Dong, H. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann. Oncol. 2016, 27, 1953–1958. [Google Scholar] [CrossRef]
- Wang, X.; Teng, F.; Kong, L.; Yu, J. PD-L1 expression in human cancers and its association with clinical outcomes. OncoTargets Ther. 2016, 9, 5023–5039. [Google Scholar] [CrossRef]
- Peng, J.; Hamanishi, J.; Matsumura, N.; Abiko, K.; Murat, K.; Baba, T.; Yamaguchi, K.; Horikawa, N.; Hosoe, Y.; Murphy, S.K.; et al. Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-kappaB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. Cancer Res. 2015, 75, 5034–5045. [Google Scholar] [CrossRef] [PubMed]
- Ikeda, S.; Okamoto, T.; Okano, S.; Umemoto, Y.; Tagawa, T.; Morodomi, Y.; Kohno, M.; Shimamatsu, S.; Kitahara, H.; Suzuki, Y.; et al. PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer. J. Thorac. Oncol. 2016, 11, 62–71. [Google Scholar] [CrossRef] [PubMed]
- Clave, S.; Pijuan, L.; Casadevall, D.; Taus, A.; Gimeno, J.; Hernandez-Llodra, S.; Rodriguez-Rivera, M.; Lorenzo, M.; Menendez, S.; Albanell, J.; et al. CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients. Histopathology 2018, 72, 259–269. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Feng, Y.; Lu, L.; Wang, H.; Dai, L.; Li, Y.; Zhang, P. Interferon-gamma-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 2012, 217, 385–393. [Google Scholar] [CrossRef] [PubMed]
- Topalian, S.L.; Taube, J.M.; Anders, R.A.; Pardoll, D.M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 2016, 16, 275–287. [Google Scholar] [CrossRef] [PubMed]
- Tsao, M.S.; Kerr, K.M.; Kockx, M.; Beasley, M.B.; Borczuk, A.C.; Botling, J.; Bubendorf, L.; Chirieac, L.; Chen, G.; Chou, T.Y.; et al. PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project. J. Thorac. Oncol. 2018, 13, 1302–1311. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blank, C.U.; Haanen, J.B.; Ribas, A.; Schumacher, T.N. CANCER IMMUNOLOGY. The “cancer immunogram”. Science 2016, 352, 658–660. [Google Scholar] [CrossRef] [PubMed]
- Allgauer, M.; Budczies, J.; Christopoulos, P.; Endris, V.; Lier, A.; Rempel, E.; Volckmar, A.L.; Kirchner, M.; von Winterfeld, M.; Leichsenring, J.; et al. Implementing tumor mutational burden (TMB) analysis in routine diagnostics-a primer for molecular pathologists and clinicians. Transl. Lung Cancer Res. 2018, 7, 703–715. [Google Scholar] [CrossRef] [PubMed]
- Schumacher, T.N.; Schreiber, R.D. Neoantigens in cancer immunotherapy. Science 2015, 348, 69–74. [Google Scholar] [CrossRef] [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]
- Gupta, D.; Heinen, C.D. The mismatch repair-dependent DNA damage response: Mechanisms and implications. DNA Repair 2019, 78, 60–69. [Google Scholar] [CrossRef] [PubMed]
- Bupathi, M.; Wu, C. Biomarkers for immune therapy in colorectal cancer: Mismatch-repair deficiency and others. J. Gastrointest. Oncol. 2016, 7, 713–720. [Google Scholar] [CrossRef] [PubMed]
- van der Burg, S.H.; Arens, R.; Ossendorp, F.; van Hall, T.; Melief, C.J. Vaccines for established cancer: Overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 2016, 16, 219–233. [Google Scholar] [CrossRef]
- Yarchoan, M.; Johnson, B.A., 3rd; Lutz, E.R.; Laheru, D.A.; Jaffee, E.M. Targeting neoantigens to augment antitumour immunity. Nat. Rev. Cancer 2017, 17, 209–222. [Google Scholar] [CrossRef]
- Keskin, D.B.; Anandappa, A.J.; Sun, J.; Tirosh, I.; Mathewson, N.D.; Li, S.; Oliveira, G.; Giobbie-Hurder, A.; Felt, K.; Gjini, E.; et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 2019, 565, 234–239. [Google Scholar] [CrossRef] [PubMed]
- Pan, R.Y.; Chung, W.H.; Chu, M.T.; Chen, S.J.; Chen, H.C.; Zheng, L.; Hung, S.I. Recent Development and Clinical Application of Cancer Vaccine: Targeting Neoantigens. J. Immunol. Res. 2018, 2018, 4325874. [Google Scholar] [CrossRef] [PubMed]
- Bais, P.; Namburi, S.; Gatti, D.M.; Zhang, X.; Chuang, J.H. CloudNeo: A cloud pipeline for identifying patient-specific tumor neoantigens. Bioinformatics 2017, 33, 3110–3112. [Google Scholar] [CrossRef] [PubMed]
- Balachandran, V.P.; Luksza, M.; Zhao, J.N.; Makarov, V.; Moral, J.A.; Remark, R.; Herbst, B.; Askan, G.; Bhanot, U.; Senbabaoglu, Y.; et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 2017, 551, 512–516. [Google Scholar] [CrossRef]
- Desai, D.V.; Kulkarni-Kale, U. T-cell epitope prediction methods: An overview. Methods Mol. Biol. 2014, 1184, 333–364. [Google Scholar] [CrossRef]
- Warren, R.L.; Choe, G.; Freeman, D.J.; Castellarin, M.; Munro, S.; Moore, R.; Holt, R.A. Derivation of HLA types from shotgun sequence datasets. Genome Med. 2012, 4, 95. [Google Scholar] [CrossRef]
- Shukla, S.A.; Rooney, M.S.; Rajasagi, M.; Tiao, G.; Dixon, P.M.; Lawrence, M.S.; Stevens, J.; Lane, W.J.; Dellagatta, J.L.; Steelman, S.; et al. Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes. Nat. Biotechnol. 2015, 33, 1152–1158. [Google Scholar] [CrossRef] [Green Version]
- Nielsen, M.; Andreatta, M. NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med. 2016, 8, 33. [Google Scholar] [CrossRef] [PubMed]
- Jurtz, V.; Paul, S.; Andreatta, M.; Marcatili, P.; Peters, B.; Nielsen, M. NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data. J. Immunol. 2017, 199, 3360–3368. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Nielsen, M.; Lund, O.; Buus, S.; Lundegaard, C. MHC class II epitope predictive algorithms. Immunology 2010, 130, 319–328. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Garijo, A.; Fajardo, C.A.; Gros, A. Determinants for Neoantigen Identification. Front. Immunol. 2019, 10, 1392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sahin, U.; Derhovanessian, E.; Miller, M.; Kloke, B.P.; Simon, P.; Lower, M.; Bukur, V.; Tadmor, A.D.; Luxemburger, U.; Schrors, B.; et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 2017, 547, 222–226. [Google Scholar] [CrossRef] [PubMed]
- Ott, P.A.; Hu, Z.; Keskin, D.B.; Shukla, S.A.; Sun, J.; Bozym, D.J.; Zhang, W.; Luoma, A.; Giobbie-Hurder, A.; Peter, L.; et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017, 547, 217–221. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, S.A.; Packard, B.S.; Aebersold, P.M.; Solomon, D.; Topalian, S.L.; Toy, S.T.; Simon, P.; Lotze, M.T.; Yang, J.C.; Seipp, C.A.; et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 1988, 319, 1676–1680. [Google Scholar] [CrossRef]
- Minkis, K.; Kavanagh, D.G.; Alter, G.; Bogunovic, D.; O’Neill, D.; Adams, S.; Pavlick, A.; Walker, B.D.; Brockman, M.A.; Gandhi, R.T.; et al. Type 2 Bias of T cells expanded from the blood of melanoma patients switched to type 1 by IL-12p70 mRNA-transfected dendritic cells. Cancer Res. 2008, 68, 9441–9450. [Google Scholar] [CrossRef]
- 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]
- Baras, A.S.; Drake, C.; Liu, J.J.; Gandhi, N.; Kates, M.; Hoque, M.O.; Meeker, A.; Hahn, N.; Taube, J.M.; Schoenberg, M.P.; et al. The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder. Oncoimmunology 2016, 5, e1134412. [Google Scholar] [CrossRef] [Green Version]
- Pages, F.; Mlecnik, B.; Marliot, F.; Bindea, G.; Ou, F.S.; Bifulco, C.; Lugli, A.; Zlobec, I.; Rau, T.T.; Berger, M.D.; et al. International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study. Lancet 2018, 391, 2128–2139. [Google Scholar] [CrossRef]
- Sakaguchi, S.; Sakaguchi, N.; Asano, M.; Itoh, M.; Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155, 1151–1164. [Google Scholar]
- Sakaguchi, S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 2004, 22, 531–562. [Google Scholar] [CrossRef] [PubMed]
- Hori, S.; Nomura, T.; Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299, 1057–1061. [Google Scholar] [CrossRef] [PubMed]
- Maeda, N.; Yoshimura, K.; Yamamoto, S.; Kuramasu, A.; Inoue, M.; Suzuki, N.; Watanabe, Y.; Maeda, Y.; Kamei, R.; Tsunedomi, R.; et al. Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients. Ann. Surg. Oncol. 2014, 21, S546–S554. [Google Scholar] [CrossRef] [PubMed]
- Limagne, E.; Euvrard, R.; Thibaudin, M.; Rebe, C.; Derangere, V.; Chevriaux, A.; Boidot, R.; Vegran, F.; Bonnefoy, N.; Vincent, J.; et al. Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen. Cancer Res. 2016, 76, 5241–5252. [Google Scholar] [CrossRef] [PubMed]
- Breitkreutz, I.; Podar, K.; Figueroa-Vazquez, V.; Wilhelm, S.; Hayden, P.J.; Anderson, K.C.; Raab, M.S. The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma. Ann. Hematol. 2018, 97, 839–849. [Google Scholar] [CrossRef]
- Krishnamoorthy, S.K.; Relias, V.; Sebastian, S.; Jayaraman, V.; Saif, M.W. Management of regorafenib-related toxicities: A review. Ther. Adv. Gastroenterol. 2015, 8, 285–297. [Google Scholar] [CrossRef]
- Ku, G.Y.; Yuan, J.; Page, D.B.; Schroeder, S.E.; Panageas, K.S.; Carvajal, R.D.; Chapman, P.B.; Schwartz, G.K.; Allison, J.P.; Wolchok, J.D. Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: Lymphocyte count after 2 doses correlates with survival. Cancer 2010, 116, 1767–1775. [Google Scholar] [CrossRef] [PubMed]
- Valpione, S.; Martinoli, C.; Fava, P.; Mocellin, S.; Campana, L.G.; Quaglino, P.; Ferrucci, P.F.; Pigozzo, J.; Astrua, C.; Testori, A.; et al. Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab. Eur. J. Cancer 2015, 51, 2086–2094. [Google Scholar] [CrossRef]
- Nakamura, Y.; Kitano, S.; Takahashi, A.; Tsutsumida, A.; Namikawa, K.; Tanese, K.; Abe, T.; Funakoshi, T.; Yamamoto, N.; Amagai, M.; et al. Nivolumab for advanced melanoma: Pretreatment prognostic factors and early outcome markers during therapy. Oncotarget 2016, 7, 77404–77415. [Google Scholar] [CrossRef] [PubMed]
- Jiang, T.; Qiao, M.; Zhao, C.; Li, X.; Gao, G.; Su, C.; Ren, S.; Zhou, C. Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: A meta-analysis. Cancer Immunol. Immunother. CII 2018, 67, 713–727. [Google Scholar] [CrossRef]
- Proctor, M.J.; McMillan, D.C.; Morrison, D.S.; Fletcher, C.D.; Horgan, P.G.; Clarke, S.J. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br. J. Cancer 2012, 107, 695–699. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, R.; Takagi, T.; Hikichi, T.; Konno, N.; Sugimoto, M.; Watanabe, K.O.; Nakamura, J.; Waragai, Y.; Kikuchi, H.; Takasumi, M.; et al. Derived neutrophil/lymphocyte ratio predicts gemcitabine therapy outcome in unresectable pancreatic cancer. Oncol. Lett. 2016, 11, 3441–3445. [Google Scholar] [CrossRef] [PubMed]
- van Kessel, K.E.; de Haan, L.M.; Fransen van de Putte, E.E.; van Rhijn, B.W.; de Wit, R.; van der Heijden, M.S.; Zwarthoff, E.C.; Boormans, J.L. Elevated Derived Neutrophil-to-Lymphocyte Ratio Corresponds With Poor Outcome in Patients Undergoing Pre-Operative Chemotherapy in Muscle-Invasive Bladder Cancer. Bladder Cancer 2016, 2, 351–360. [Google Scholar] [CrossRef] [Green Version]
- Ferrucci, P.F.; Ascierto, P.A.; Pigozzo, J.; Del Vecchio, M.; Maio, M.; Antonini Cappellini, G.C.; Guidoboni, M.; Queirolo, P.; Savoia, P.; Mandala, M.; et al. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: Prognostic relevance in metastatic melanoma patients receiving ipilimumab. Ann. Oncol. 2016, 27, 732–738. [Google Scholar] [CrossRef]
- Talaiezadeh, A.; Shahriari, A.; Tabandeh, M.R.; Fathizadeh, P.; Mansouri, S. Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues. Cancer Cell Int. 2015, 15, 19. [Google Scholar] [CrossRef] [PubMed]
- Wong, N.; De Melo, J.; Tang, D. PKM2, a Central Point of Regulation in Cancer Metabolism. Int. J. Cell Biol. 2013, 2013, 242513. [Google Scholar] [CrossRef] [PubMed]
- Balch, C.M.; Gershenwald, J.E.; Soong, S.J.; Thompson, J.F.; Atkins, M.B.; Byrd, D.R.; Buzaid, A.C.; Cochran, A.J.; Coit, D.G.; Ding, S.; et al. Final version of 2009 AJCC melanoma staging and classification. J. Clin. Oncol. 2009, 27, 6199–6206. [Google Scholar] [CrossRef] [PubMed]
- Jing, X.; Huang, C.; Zhou, H.; Li, C.; Fan, L.; Chen, J.; Zhang, G.; Liu, Y.; Cui, Z.; Qi, D.; et al. Association between serum C-reactive protein value and prognosis of patients with non-small cell lung cancer: A meta-analysis. Int. J. Clin. Exp. Med. 2015, 8, 10633–10639. [Google Scholar] [PubMed]
- Stevens, L.; Pathak, S.; Nunes, Q.M.; Pandanaboyana, S.; Macutkiewicz, C.; Smart, N.; Smith, A.M. Prognostic significance of pre-operative C-reactive protein and the neutrophil-lymphocyte ratio in resectable pancreatic cancer: A systematic review. HPB 2015, 17, 285–291. [Google Scholar] [CrossRef] [PubMed]
- Woo, H.D.; Kim, K.; Kim, J. Association between preoperative C-reactive protein level and colorectal cancer survival: A meta-analysis. Cancer Causes Control. 2015, 26, 1661–1670. [Google Scholar] [CrossRef] [PubMed]
- Akamine, T.; Takada, K.; Toyokawa, G.; Kinoshita, F.; Matsubara, T.; Kozuma, Y.; Haratake, N.; Takamori, S.; Hirai, F.; Tagawa, T.; et al. Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers. Surg. Oncol. 2018, 27, 88–94. [Google Scholar] [CrossRef] [PubMed]
- Shrotriya, S.; Walsh, D.; Bennani-Baiti, N.; Thomas, S.; Lorton, C. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review. PLoS ONE 2015, 10, e0143080. [Google Scholar] [CrossRef]
- Steffens, S.; Kohler, A.; Rudolph, R.; Eggers, H.; Seidel, C.; Janssen, M.; Wegener, G.; Schrader, M.; Kuczyk, M.A.; Schrader, A.J. Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients. BMC Cancer 2012, 12, 399. [Google Scholar] [CrossRef]
- Bernhardt, D.; Aufderstrasse, S.; Konig, L.; Adeberg, S.; Bozorgmehr, F.; Christopoulos, P.; Shafie, R.A.E.; Horner-Rieber, J.; Kappes, J.; Thomas, M.; et al. Impact of inflammatory markers on survival in patients with limited disease small-cell lung cancer undergoing chemoradiotherapy. Cancer Manag. Res. 2018, 10, 6563–6569. [Google Scholar] [CrossRef]
- Zaharie, F.; Muresan, M.S.; Petrushev, B.; Berce, C.; Gafencu, G.A.; Selicean, S.; Jurj, A.; Cojocneanu-Petric, R.; Lisencu, C.I.; Pop, L.A.; et al. Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer. J. Gastrointest. Liver Dis. JGLD 2015, 24, 435–443. [Google Scholar] [CrossRef] [Green Version]
- Shindo, Y.; Hazama, S.; Nakamura, Y.; Inoue, Y.; Kanekiyo, S.; Suzuki, N.; Takenouchi, H.; Tsunedomi, R.; Nakajima, M.; Ueno, T.; et al. miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer. Oncol. Lett. 2017, 14, 1355–1362. [Google Scholar] [CrossRef]
- Iorio, M.V.; Ferracin, M.; Liu, C.G.; Veronese, A.; Spizzo, R.; Sabbioni, S.; Magri, E.; Pedriali, M.; Fabbri, M.; Campiglio, M.; et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65, 7065–7070. [Google Scholar] [CrossRef]
- Schetter, A.J.; Leung, S.Y.; Sohn, J.J.; Zanetti, K.A.; Bowman, E.D.; Yanaihara, N.; Yuen, S.T.; Chan, T.L.; Kwong, D.L.; Au, G.K.; et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008, 299, 425–436. [Google Scholar] [CrossRef]
- Nagao, Y.; Hisaoka, M.; Matsuyama, A.; Kanemitsu, S.; Hamada, T.; Fukuyama, T.; Nakano, R.; Uchiyama, A.; Kawamoto, M.; Yamaguchi, K.; et al. Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma. Mod. Pathol. 2012, 25, 112–121. [Google Scholar] [CrossRef]
- Li, X.; Nie, J.; Mei, Q.; Han, W.D. MicroRNAs: Novel immunotherapeutic targets in colorectal carcinoma. World J. Gastroenterol. 2016, 22, 5317–5331. [Google Scholar] [CrossRef]
- Beg, M.S.; Brenner, A.J.; Sachdev, J.; Borad, M.; Kang, Y.K.; Stoudemire, J.; Smith, S.; Bader, A.G.; Kim, S.; Hong, D.S. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Investig. New Drugs 2017, 35, 180–188. [Google Scholar] [CrossRef]
- Wang, Z.; Liu, Y.; Zhang, Y.; Shang, Y.; Gao, Q. MDSC-decreasing chemotherapy increases the efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma and pancreatic cancer. Oncotarget 2016, 7, 4760–4769. [Google Scholar] [CrossRef]
- Ghiringhelli, F.; Larmonier, N.; Schmitt, E.; Parcellier, A.; Cathelin, D.; Garrido, C.; Chauffert, B.; Solary, E.; Bonnotte, B.; Martin, F. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur. J. Immunol. 2004, 34, 336–344. [Google Scholar] [CrossRef]
- Kunisada, Y.; Eikawa, S.; Tomonobu, N.; Domae, S.; Uehara, T.; Hori, S.; Furusawa, Y.; Hase, K.; Sasaki, A.; Udono, H. Attenuation of CD4(+)CD25(+) Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug. EBioMedicine 2017, 25, 154–164. [Google Scholar] [CrossRef]
- Veltman, J.D.; Lambers, M.E.; van Nimwegen, M.; Hendriks, R.W.; Hoogsteden, H.C.; Aerts, J.G.; Hegmans, J.P. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 2010, 10, 464. [Google Scholar] [CrossRef]
- Zheng, Y.; Xu, M.; Li, X.; Jia, J.; Fan, K.; Lai, G. Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Mol. Immunol. 2013, 54, 74–83. [Google Scholar] [CrossRef]
- Philip, M.; Schietinger, A. Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections. Curr. Opin. Immunol. 2019, 58, 98–103. [Google Scholar] [CrossRef]
- Blackburn, S.D.; Shin, H.; Haining, W.N.; Zou, T.; Workman, C.J.; Polley, A.; Betts, M.R.; Freeman, G.J.; Vignali, D.A.; Wherry, E.J. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 2009, 10, 29–37. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Jia, H. Metagenome-wide association studies: Fine-mining the microbiome. Nat. Rev. Microbiol. 2016, 14, 508–522. [Google Scholar] [CrossRef]
- Picardo, S.L.; Coburn, B.; Hansen, A.R. The microbiome and cancer for clinicians. Crit. Rev. Oncol. Hematol. 2019, 141, 1–12. [Google Scholar] [CrossRef]
- Rubinstein, M.R.; Wang, X.; Liu, W.; Hao, Y.; Cai, G.; Han, Y.W. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 2013, 14, 195–206. [Google Scholar] [CrossRef]
- Tahara, T.; Yamamoto, E.; Suzuki, H.; Maruyama, R.; Chung, W.; Garriga, J.; Jelinek, J.; Yamano, H.O.; Sugai, T.; An, B.; et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 2014, 74, 1311–1318. [Google Scholar] [CrossRef] [PubMed]
- Abed, J.; Emgard, J.E.; Zamir, G.; Faroja, M.; Almogy, G.; Grenov, A.; Sol, A.; Naor, R.; Pikarsky, E.; Atlan, K.A.; et al. Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc. Cell Host Microbe 2016, 20, 215–225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamaoka, Y.; Suehiro, Y.; Hashimoto, S.; Hoshida, T.; Fujimoto, M.; Watanabe, M.; Imanaga, D.; Sakai, K.; Matsumoto, T.; Nishioka, M.; et al. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J. Gastroenterol. 2018, 53, 517–524. [Google Scholar] [CrossRef]
Sample | Biomarker | Clinical Significance |
---|---|---|
Tumor Tissue | PD-L1 | Increased expression in tumor cells is associated with a positive clinical response to anti-PD-1/PD-L1 antibodies [16,21,22,23,24,25]. |
TMB | High TMB is associated with an improved response to ICIs [26,27]. | |
MMR | MMR deficiency, regardless of tumor types, correlates with a clinical response to pembrolizumab [28,29,30,31,32,33]. | |
TIL | The presence of tumor-infiltrating CD8+ T cells is associated with a better prognosis [34,35,36,37,38,39]. | |
Tregs/ MDSCs | The presence of tumor-infiltrating Tregs and MDSCs is associated with a poor prognosis [40,41,42,43,44,45,46]. | |
Peripheral Blood | Neutrophils/leukocytes | Elevated NLR is associated with a poor response [7,47,48,49,50]. |
Low % of lymphocytes | Patients with a lymphocyte count less than 15% should be excluded from immunotherapy [7]. | |
LDH | Elevated pretreatment levels are correlated with a worse OS [51,52,53,54,55,56,57,58,59]. | |
CRP | High level of CRP is associated with an increased risk of OS [60]. | |
miRNA | Expression of several miRNAs is associated with clinical outcomes [61,62]. | |
Tregs/ MDSCs | Decreased level of circulating Tregs and MDSCs after treatment correlated with improved prognosis [6,60,63]. | |
Ki-67 expression | Increased Ki-67 expression in PD1+ CD8+ T cells is associated with a good response [64,65]. | |
Feces | Microbiome | The presence of Ruminococcaceae/Faecalibacterium in melanoma patients and Akkermansia muciniphila in NSCLC and RCC is associated with a clinical response to anti-PD-1 antibody [66,67]. |
Trial Number | Phase | Disease | Strategy | Sponsor/Investigator |
---|---|---|---|---|
NCT03639714 | 1/2 | NSCLC, CRC, Gastroesophageal cancer, Urothelial cancer | Adenovirus vector | Gritstone Oncology, Inc. |
NCT03313778 | 1 | Solid tumors | mRNA | ModernaTX, Inc. |
NCT03871205 | 1 | Lung cancer | DC | Shenzhen People’s Hospital/Lili Ren |
NCT03674073 | 1 | HCC | DC | Chinese PLA General Hospital/Ping Liang |
NCT02956551 | 1 | NSCLC | DC | Sichuan University/Zhen-YU Ding |
NCT03532217 | 1 | Prostate cancer | DNA | Washington University School of Medicine/Russell Pachynski |
NCT03122106 | 1 | Pancreatic cancer | DNA | Washington University School of Medicine/Gillanders et al. |
NCT03199040 | 1 | Breast cancer | DNA | Washington University School of Medicine/William Gillanders |
NCT04015700 | 1 | Glioblastoma | DNA | Washington University School of Medicine/Gavin Dunn |
NCT03988283 | 1 | Pediatric recurrent brain tumor | DNA | Washington University School of Medicine/Karen M Gauvain |
NCT03645148 | 1 | Pancreatic cancer | Peptide | Zhejiang Provincial People’s Hospital |
NCT03558945 | 1 | Pancreatic cancer | Peptide | Changhai Hospital/Gang Jin |
NCT03662815 | 1 | Advanced solid tumor | Peptide | Sir Run Run Shaw Hospital |
NCT03715985 | 1 | Melanoma, NSCLC, Renal cell carcinoma | Peptide | Herlev Hospital/Inge Marie Svane |
NCT02950766 | 1 | Renal cell carcinoma | Peptide | Patrick Ott |
NCT03422094 | 1 | Glioblastoma | Peptide | Washington University School of Medicine/Gavin Dunn |
NCT03361852 | 1 | Follicular lymphoma | Peptide | Dana-Farber Cancer Institute/Eric Jacobsen |
NCT03929029 | 1 | Melanoma | Peptide | Dana-Farber Cancer Institute/Patrick A Ott |
NCT03068832 | 1 | Pediatric brain tumor | Peptide | Washington University School of Medicine/Karen M Gauvain |
NCT03606967 | 2 | Breast cancer | Peptide | National Cancer Institute/William Gillanders |
NCT03219450 | 1 | Lymphocytic leukemia | Peptide | Dana-Farber Cancer Institute/Pavan Bachireddy |
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Shindo, Y.; Hazama, S.; Tsunedomi, R.; Suzuki, N.; Nagano, H. Novel Biomarkers for Personalized Cancer Immunotherapy. Cancers 2019, 11, 1223. https://doi.org/10.3390/cancers11091223
Shindo Y, Hazama S, Tsunedomi R, Suzuki N, Nagano H. Novel Biomarkers for Personalized Cancer Immunotherapy. Cancers. 2019; 11(9):1223. https://doi.org/10.3390/cancers11091223
Chicago/Turabian StyleShindo, Yoshitaro, Shoichi Hazama, Ryouichi Tsunedomi, Nobuaki Suzuki, and Hiroaki Nagano. 2019. "Novel Biomarkers for Personalized Cancer Immunotherapy" Cancers 11, no. 9: 1223. https://doi.org/10.3390/cancers11091223