REFERENCES
1. Mansfield AS, Nevala WK, Leiser EA, Leontovich AA, Markovic SN. The immunomodulatory effects of bevacizumab on systemic immunity in patients with metastatic melanoma. Oncoimmunology 2013;2:e24436.
2. Emmett MS, Dewing D, Pritchard-Jones RO. Angiogenesis and melanoma - from basic science to clinical trials. Am J Cancer Res 2011;1:852-68.
5. Tas F. Metastatic behavior in melanoma: timing, pattern, survival, and influencing factors. J Oncol 2012;2012:647684.
6. Carbone PP, Costello W. Eastern cooperative oncology group studies with DTIC (NSC-45388). Cancer Treat Rep 1976;60:193-8.
7. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105-16.
8. Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol 2017;14:463-82.
9. Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016;315:1600-9.
10. Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:1270-1.
11. Schachter JRA, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival analysis of KEYNOTE-006. Lancet Oncol 2017;390:1853-62.
12. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015;33:1889-94.
13. La-Beck NM, Jean GW, Huynh C, Alzghari SK, Lowe DB. Immune checkpoint inhibitors: new insights and current place in cancer therapy. Pharmacotherapy 2015;35:963-76.
14. Ehrlich P. Collected papers in four volumes including a complete bibliography. London: Pergamon Press; 1956.
16. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991-8.
17. Schreiber RD, Old LD, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011;331:1565-70.
18. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996;271:1734-6.
20. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO 1992;11:3887-95.
21. Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol 2017;18:e731-41.
22. O’Donnell JS, Long GV, Scolyer RA, Teng MW, Smyth MJ. Resistance to PD/PDL1 checkpoint inhibition. Cancer Treat Rev 2017;52:71-81.
23. Ribas A, Shin DS, Zaretsky J, Frederiksen J, Cornish A, et al. PD-1 blockade expands intratumoral memory T cells. Cancer Immunol Res 2016;4:194-203.
24. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704.
25. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182:459-65.
26. Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, et al. A new member of the immunoglobulin superfamily--CTLA-4. Nature 1987;328:267-70.
27. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64.
28. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 2015;160:48-61.
29. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 2016;375:819-29.
30. Zhao F, Sucker A, Horn S, Heeke C, Bielefeld N, et al. Melanoma lesions independently acquire T-cell resistance during metastatic latency. Cancer Res 2016;76:4347-58.
31. Wang X, Schoenhals JE, Li A, Valdecanas DR, Ye H, et al. Suppression of type I IFN signaling in tumors mediates resistance to anti-PD-1 treatment that can be overcome by radiotherapy. Cancer Res 2017;77:839-50.
32. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 2012;482:400-4.
33. Verdegaal EM, de Miranda NF, Visser M, Harryvan T, van Buuren MM, et al. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature 2016;536:91-5.
34. Arenas-Ramirez N, Sahin D, Boyman O. Epigenetic mechanisms of tumor resistance to immunotherapy. Cell Mol Life Sci 2018;75:4163-76.
35. Pitt JM, Vetizou M, Daillere R, Roberti MP, Yamazaki T, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumour-intrinsic and -extrinsic factors. Immunity 2016;44:1255-69.
36. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23.
37. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26.
38. Weber JS, D’Angelo SP, Minor D, Hodi FS, Gutzmer R, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375-84.
39. Robert C, Long GV, Brady B, Dutriaux C, Maio M, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015;372:320-30.
40. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122-33.
41. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2017;377:1345-56.
42. Long GV, Schachter J, Ribas A, Arance AM, Grob JJ, et al. 4-year survival and outcomes after cessation of pembrolizumab (pembro) after 2-years in patients (pts) with ipilimumab (ipi)-naïve advanced melanoma in KEYNOTE-006. J Clin Oncol 2018;36:Abstract 9503.
43. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomized, double-blind, phase 3 trial. Lancet Oncol 2015;16:522-30.
44. Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018;378:1789-801.
45. Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, et al. CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017;377:1824-35.
46. Robert C, Schachter J, Long GV, Arance A, Grob JJ, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521-32.
47. Robert C, Ribas A, Hamid O, Daud A, Wolchok JD, et al. Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. J Clin Oncol 2016;34:abstr 9503.
48. Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016;315:1600-9.
49. Carlino MS, Atkinson V, Cebon JS. KEYNOTE-029: efficacy and safety of pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma. J Clin Oncol 2017;35:9545.
50. Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 2016;17:1558-68.
51. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
52. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive and acquired resistance to cancer immunotherapy. Cell 2017;168:707-23.
53. Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 2018;118:9-16.
54. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014;515:577-81.
55. Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000;74:181-273.
56. Sucker A, Zhao F, Real B, Heeke C, Bielefeld N, et al. Genetic evolution of T-cell resistance in the course of melanoma progression. Clin Cancer Res 2014;20:6593-604.
57. D’Urso CM, Wang ZG, Cao Y, Tatake R, Zeff RA, et al. Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. J Clin Invest 1991;87:284-92.
58. Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, et al. Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst 1996;88:100-8.
59. Ward PL, Koeppen HK, Hurteau T, Rowley DA, Schreiber H. Major histocompatibility complex class I and unique antigen expression by murine tumors that escaped from CD8+ T-cell-dependent surveillance. Cancer Res 1990;50:3851-8.
60. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 2015;350:207-11.
61. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013;499:214-8.
62. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, et al. Mismatch-repair deficiency predicts response of solid tumours to PD-1 blockade. Science 2017;357:409-13.
63. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, et al. PD-1 blockade in tumours with mismatch-repair deficiency. N Engl J Med 2015;372:2509-20.
64. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014;371:2189-99.
65. McGranahan N, Furness AJS, Rosenthal R, Ramskov S, Lyngaa R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016;351:1463-9.
66. Reuben A, Spencer CN, Prieto PA, Gopalakrishnan V, Reddy SM, et al. Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med 2017;2:10.
67. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415-21.
68. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.
69. Coulie PG, Van den Eynde JB, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 2014;14:135-46.
70. Martin AM, Nirschl TR, Nirschl CJ, Francica BJ, Kochel CM, et al. Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance. Prostate Cancer Prostatic Dis 2015;18:325-32.
71. Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep 2016;15:857-65.
72. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 2002;188:22-32.
73. James SR, Link PA, Karpf AR. Epigenetic regulation of X-linked cancer/germline antigen genes by DNMT1 and DNMT3b. Oncogene 2006;25:6975-85.
74. Yu J, Zhang H, Gu J, Lin S, Li J, et al. Methylation profiles of thirty four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma. BMC Cancer 2004;4:65.
75. Yu J, Ni M, Xu J, Zhang H, Gao B, et al. Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis. BMC Cancer 2002;2:29.
76. Andersen MH, Becker JC, Straten PT. Regulators of apoptosis: suitable targets for immune therapy of cancer. Nat Rev Drug Discov 2005;4:399-409.
77. Peng W, Chen JQ, Liu C, Malu S, Creasy C, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov 2016;6:202-16.
78. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nature Rev Immunol 2005;5:375-86.
79. Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell 2016;167:1540-54.e12.
80. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001;410:1107-11.
81. Gao J, Shi LZ, Zhao H, Chen J, Xiong L, et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 2016;167:397-404.
82. Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov 2017;7:188-201.
83. Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB, et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 2017;547:413-8.
84. Hopkins-Donaldson S, Ziegler A, Kirtz S, Bigosch C, Kandioler D, et al. Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ 2003;10:356-64.
85. Eramo A, Pallini R, Lotti F, Sette G, Patti M, et al. Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction. Cancer Res 2005;65:11469-77.
86. Hugo W, Shi H, Sun L, Piva M, Song C, et al. Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell 2015;162:1271-85.
87. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell ;165:35-44.
88. Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest 2017;127:2930-40.
89. Falletta P, Sanchez-del-Campo L, Chauhan J, Effern M, Kenyon A, et al. Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma. Genes Dev 2017;31:18-33.
90. Shayan G, Srivastava R, Li J, Schmitt N, Kane LP, et al. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer. Oncoimmunology 2016;6:e1261779.
91. Huang RY, Francois A, McGray AR, Miliotto A, Odunsi K. Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer. Oncoimmunology 2016;6:e1249561.
92. Koyama S, Akbay EA, Li YY, Herter-Spri GS, Buczkowski KA, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun 2016;17:10501.
93. Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, et al. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med 2017;23:551-5.
94. Thommen DS, Schreiner J, Muller P, Herzig P, Roller A, 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;3:1344-55.
95. Rao SV, Moran AE, Graff JN. Predictors of response and resistance to checkpoint inhibitors in solid tumors. Ann Transl Med 2017;5:468.
96. Pullari B, Kumar A, Shaheen M, Jeter J, Sundarajan S. Tumor microenvironment changes leading to resistance of immune checkpoint inhibitors in metastatic melanoma and strategies to overcome resistance. Pharmacol Res 2017;123:95-102.
97. Chen W, Ten Dijke P. Immunoregulation by members of the TGFβ superfamily. Nat Rev Immunol 2016;16:723-40.
98. Powderly JD, Koeppen H, Hodi FS, Sosman JA, Gettinger SN, et al. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. J Clin Oncol 2013;31:abstr 3001.
99. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017;541:321-30.
100. Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, et al. Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in melanoma. Clin Cancer Res 2017;23:5024-33.
101. Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 2015;523:231-5.
102. Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 2016;354:1160-5.
103. Sen DR, Kaminski J, Barnitz RA, Kurachi M, Gerdemann U, et al. The epigenetic landscape of T cell exhaustion. Science 2016;354:1165-9.
104. Ngiow SF, Young A, Blake SJ, Hill GR, Yagita H, et al. Agonistic CD40 mAb-driven IL12 reverses resistance to anti-PD1 in a T-cell-rich tumor. Cancer Res 2016;76:6266-77.
105. Mognol GP, Spreafico R, Wong V, Scott-Browne JP, Togher S, et al. Exhaustion-associated regulatory regions in CD8 + tumor-infiltrating T cells. Proc Natl Acad Sci USA 2017;114:E2776-85.
106. Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 2017;545:60-5.
107. Łuksza M, Riaz N, Makarov V, Balachandran VP, Hellmann MD, et al. A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature 2017;551:517-20.
108. Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 2017;551:512-6.
109. Galluzzi L, Vitale E, Aaronson SA, Abrams JM, Adam DP, et al. Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 2018;25:486-541.
110. Roh W, Chen PL, Reuben A, Spencer CN, Prieto PA, et al. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med 2017;9:eaah3560.
111. Winograd R, Byrne KT, Evans RA, Odorizzi PM, Meyer AR, et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol Res 2015;3:399-411.
112. Ni K, O’Neill HC. The role of dendritic cells in T cell activation. Immunol Cell Biol 1997;75:223-30.
113. Korkolopoulou P, Kaklamanis L, Pezzella F, Harris AL, Gatter KC. Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 1996;73:148-53.
114. Kelderman S, Schumacher TN, Haanen JB. Acquired and intrinsic resistance in cancer immunotherapy. Mol Oncol 2014;8:1132-9.
115. Restifo NP, Smyth MJ, Snyder A. Acquired resistance to immunotherapy and future challenges. Nat Rev Cancer 2016;16:121-6.
116. Jager E, Ringhoffer M, Altmannsberger M, Arand M, Karbach J, et al. Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer 1997;71:142-7.
117. Wu W, Wang W, Wang Y, Li W, Yu G, et al. IL-37b suppresses T cell priming by modulating dendritic cell maturation and cytokine production via dampening ERK/NF-kappaB/S6K signalings. Acta Biochim Biophys Sin (Shanghai) 2015;47:597-603.
118. Emeagi PU, Maenhout S, Dang N, Heirman C, Thielemans K, et al. Downregulation of Stat3 in melanoma: reprogramming the immune microenvironment as an anticancer therapeutic strategy. Gene Ther 2013;20:1085-92.
119. Chattopadhyay G, Shevach EM. Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. J Immunol 2013;191:5875-84.
120. Hargadon KM, Bishop JD, Brandt JP, Hand ZC, Ararso YT, et al. Melanoma-derived factors alter the maturation and activation of differentiated tissue-resident dendritic cells. Immunol Cell Biol 2016;94:24-38.
121. Lindenberg JJ, van de Ven R, Lougheed SM, Zomer A, Santegoets SJAM, et al. Functional characterization of a STAT3-dependent dendritic cell-derived CD14+ cell population arising upon IL-10-driven maturation. OncoImmunology 2013;2:e23837.
122. Hong M, Puaux AL, Huang C, Loumagne L, Tow C, et al. Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. Cancer Res 2011;71:6997-7009.
123. Liu C, Peng W, Xu C, Lou Y, Zhang M, et al. BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice. Clin Cancer Res 2013;19:393-403.
124. Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 2017;31:711-23.
125. Massi D, Romano E, Rulli E, Merelli B, Nassini R, et al. Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients. Eur J Cancer 2017;78:70-81.
126. van Vierken LE, Kiefer CM, Morehouse C, Li Y, Groves C, et al. EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter. Stem Cells Transl Med 2013;2:43-52.
127. Adhikary G, Grun D, Balasubramanian S, Kerr C, Huang JM, et al. Survival of skin cancer stem cells requires the Ezh2 polycomb group protein. Carcinogenesis 2015;36:800-10.
128. Zingg D, Debbache J, Schaefer SM, Tuncer E, Frommer SC, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun 2015;6:6051.
129. Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 2008;27:7274-84.
130. Ma DN, Chai ZT, Zhu XD, Zhang N, Zhan DH, et al. MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2. J Hematol Oncol 2016;9:1.
131. Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature 2015;527:249-53.
132. Nagarsheth N, Peng D, Kryczek I, Wu K, Li W, et al. PRC2 epigenetically silences Th1-type chemokines to suppress effector T-cell trafficking in colon cancer. Cancer Res 2016;76:275-82.
133. Zingg D, Arenas-Ramirez N, Sahin D, Rosalia RA, Antunes AT, et al. The histone methyltransferase Ezh2 controls mechanisms of adaptive resistance to tumor immunotherapy. Cell Rep 2017;20:854-67.
134. Oida T, Zhang X, Goto M, Hachimura S, Totsuka M, et al. CD4+CD25− T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism. J Immunol 2003;170:2516-22.
135. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008;133:775-87.
136. Sundstedt A, O’Neill EJ, Nicolson KS, Wraith DC. Role for IL-10 in suppression mediated by peptide-induced regulatory T cells in vivo. J Immunol 2003;170:1240-8.
137. Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, et al. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood 2015;125:1061-72.
138. Guo F, Wang Y, Liu J, Mok SC, Xue F, et al. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 2015;35:816-26.
139. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med 2009;206:1327-37.
140. Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006;203:871-81.
141. Le DT, Lutz E, Uram JN, Sugar EA, Onners B, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 2013;36:382-9.
142. Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res 2014;74:5057-69.
143. Meyer C, Cagnon L, Costa-Nunes CM, Baumgaertner P, Montandon N, et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 2014;63:247-57.
144. De Henau O, Rausch M, Winkler D, Campesato LF, Liu C, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells. Nature 2016;539:443-7.
145. Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, et al. PI3Kgamma is a molecular switch that controls immune suppression. Nature 2016;539:437-42.
146. Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 2018;554:544-8.
147. Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, et al. TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 2018;554:538-43.
148. Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, et al. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy. Nat Commun 2018;9:741.
149. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003;348:203-13.
150. Schaaf MB, Garg AD, Agostinis P. Defining the role of the tumor vasculature in antitumor immunity and immunotherapy. Cell Death Dis 2018;9:115.
151. Motz GT, Santoro SP, Wang LP, Garrabrant T, Lastra RR, et al. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 2014;20:607-15.
152. Demunter A, De Wolf-Peeters C, Degreef H, Stas M, van den Oord JJ. Expression of the endothelin-B receptor in pigment cell lesions of the skin. Evidence for its role as tumor progression marker in malignant melanoma. Virchows Arch 2001;438:485-91.
153. Buckanovich RJ, Facciabene A, Kim S, Benencia F, Sasaroli D, et al. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med 2008;14:28-36.
154. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumor activity. Nat Rev Cancer 2008;8:579-91.
155. Young MR, Wright MA, Coogan M, Young ME, Bagash J. Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor beta. Cancer Immunol Immunother 1992;35:14-8.
156. Commeren DL, Van Soest PL, Karimi K, Lowenberg B, Cornelissen JJ, et al. Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells. Immunology 2003;110:188-96.
157. Delgoffe GM. Filling the tank: keeping antitumor T cells metabolically fit for the long haul. Cancer Immunol Res 2016;4:1001-6.
158. Barsoum IB, Smallwood CA, Siemens DR, Graham CH. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res 2014;74:665-74.
159. Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, et al. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity 2016;45:701-3.
160. Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab 2016;24:657-71.
161. Young A, Mittal D, Stagg H, Smyth MH. Targeting cancer-derived adenosine: new therapeutic approaches. Cancer Discov 2014;4:879-88.
162. Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The “cancer immunogram”. Science 2016;352:658-60.
163. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 2017;109:3812-9.
164. Weide B, Martens A, Hassel JC, Berking C, Postow MA, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res 2016;22:5487-96.
165. Diem S, Kasenda B, Spain L, Martin-Liberal J, Marconcini R, et al. Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer 2016;114:256-61.
166. Zimmer L, Apuri S, Eroglu Z, Kottschade LA, Forschner A, et al. Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. Eur J Cancer 2017;75:47-55.
167. Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 2001;7:1118-22.
168. Grohmann U, Fallarino F, Puccetti P. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 2003;24:242-8.
169. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942-9.
170. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, 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;64:5839-49.
171. Platten M, von Knebel Doeberitz N, Oezen I, Wick W, Ochs K. Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front Immunol 2015;5:673.
172. Mondanelli G, Bianchi R, Pallotta MT, Orabona C, Albini E, et al. A relay pathway between arginine and tryptophan metabolism confers immunosuppressive properties on dendritic cells. Immunity 2017;46:233-44.
173. Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med 2013;210:1389-402.
174. Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep 2015;13:412-24.
175. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003;9:1269-74.
176. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, et al. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999;189:1363-72.
177. Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 2013;5:200ra116.
178. Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, et al. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J Immunol Ther Cancer 2014;2:3.
179. Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 2018;8:403-16.
180. Mitsuhashi D, Nosho K, Sukawa Y, Matsunaga Y, Ito M, et al. Association of Fusobacteriumspecies in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 2015;6:7209-20.
181. Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog 2017;13:e1006480.
182. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015;350:1084-9.
183. Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015;350:1079-84.
184. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 2005;122:107-18.
185. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008;453:620-5.
186. Osherov N, Ben-Ami R. Modulation of host angiogenesis as a microbial survival strategy and therapeutic target. PLoS Pathog 2016;12:e1005479-8.
187. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012;491:254-8.
188. Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, et al. Binding of the Fap2 protein of fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 2015;42:344-55.
189. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013;14:207-15.
190. Takeda K, Nakayama M, Hayakawa Y, Kojima Y, Ikeda H, et al. IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting. Nat Commun 2017;8:14607.
191. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov 2017;7:264-76.
192. Pereira C, Gimenez-Xavier P, Pros E, Pajares MJ, Moro M, et al. Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition. Clin Cancer Res 2016;23:3203-13.
193. Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: biology, design and application. Trends Immunol 2015;36:763-77.
194. Arenas-Ramirez N, Zou C, Popp S, Zingg D, Brannetti B, et al. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci Transl Med 2016;8:367ra166.
195. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015;27:450-61.
197. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res 2013;19:1021-34.
198. Gide TN, Wilmott JS, Scolyer RA, Long GV. Primary and acquired resistance to immune checkpoint inhibitors in metastatic melanoma. Clin Cancer Res 2018;24:1260-70.
199. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015;15:486-99.
200. Shin H, Wherry EJ. CD8 T cell dysfunction during chronic viral infection. Curr Opin Immunol 2007;19:408-15.
201. Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang NAS, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell 2017;170:1120-33.e17.
202. Sade-Feldman M, Yizhak K, Bjorgaard SL, Ray JP, de Boer CG, et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 2018;175:998-1013.
203. Kurtulus S, Madi A, Escobar G, Klapholz M, Nyman J, et al. Checkpoint blockade immunotherapy induces dynamic changes in PD-1-CD8+ tumor-infiltrating T cells. Immunity 2019;50:181-94.
204. Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 2017;28:1368-79.
205. Wargo JA, Gopalakrishnan V, Spencer C, Karpinets T, Reuben A, et al. Association of the diversity and composition of the gut microbiome with responses and survival (PFS) in metastatic melanoma (MM) patients (pts) on anti-PD-1 therapy. J Clin Oncol 2017;35:abstr3008.
206. Derosa L, Routy B, Enot D, Baciarello G, Massard C, et al. Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Proc Am Soc Clin Oncol 2017;35:abstr462.
207. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015;350:1079-84.
208. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and anticancer immunosurveillance. Cell 2016;165:276-87.
209. Humphries A, Daud A. The gut microbiota and immune checkpoint inhibitors. Hum Vaccin Immunother 2018;14:2178-82.
210. McQuade JL, Gopalakrishnan V, Spencer C, Andrews MC, Helmink B, et al. The gut microbiome of melanoma patients is distinct from that of healthy individuals and is impacted by probiotic and antibiotic use. SMR Congress Abstracts 2018.
211. Valpione S, Martinoli C, Fava P, Mocillin S, Capgana LG, et al. Personalised medicine: development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab. Eur J Cancer 2015;51:2086-94.
212. Nishino M, Giobbie-Hurder A, Manos MP, Bailey N, Buchbinder EI, et al. Immune-related tumor response dynamics in melanoma patients treated with pembrolizumab: identifying markers for clinical outcome and treatment decisions. Clin Cancer Res 2017;23:4671-9.
213. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568-71.
214. Corrales L, McWhirter SM, Dubensky TW Jr, Gajewski TF. The host STING pathway at the interface of cancer and immunity. J Clin Invest 2016;126:2404-11.
215. Fu H, Kishore M, Gittens B, Wang G, Coe D, et al. Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation. Nat Commun 2014;5:3436.
216. Lee JM, Cimino-Mathews A, Peer CJ, Zimmer A, Lipkowitz S, et al. Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-ribose) polymerase inhibitor olaparib or vascular endothelial growth factor receptor 1-3 inhibitor cediranib in women’s cancers: a dose-escalation, phase I study. J Clin Oncol 2017;35:2193-202.
217. Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun 2016;7:12624.
218. Bouzin C, Brouet A, De Vriese J, DeWever J, Feron O. Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin-1 and nitric oxide as control points of endothelial cell anergy. J Immunol 2007;178:1505-11.
219. Terme M, Pernot S, Marcheteau E, Sandoval F, Benhamouda N, et al. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res 2013;73:539-49.
220. Smith HA, Cronk RJ, Lang JM, McNeel DG. Expression and immunotherapeutic targeting of the SSX family of cancer-testis antigens in prostate cancer. Cancer Res 2011;71:6785-95.
221. Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, et al. Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2′-deoxycytidine. Cancer Res 1994;54:1766-71.
222. Dubovsky JA, McNeel DG. Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor. Prostate 2007;67:1781-90.
223. Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood 2010;116:1908-18.
224. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012;72:917-27.
225. Foy SP, Sennino B, dela Cruz T, Cote JJ, Gordon EJ, et al. Poxvirus-based active immunotherapy with PD-1 and LAG-3 dual immune checkpoint inhibition overcomes compensatory immune regulation, yielding complete tumor regression in mice. PLoS One 2016;11:e0150084.
226. Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, et al. Anti-TIM3 antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses established tumors. Cancer Res 2011;71:3540-51.
227. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2010;207:2187-94.
228. Heninger E, Krueger TE, Lang JM. Augmenting antitumor immune responses with epigenetic modifying agents. Front Immunol 2015;6:29.
229. Gangadhar TC, Hamid O, Smith DC, Bauer TM, Wasser JS, et al. Epacadostat plus pembrolizumab in patients with advanced melanoma and select solid tumors: updated phase 1 results from ECHO-202/KEYNOTE-037. Ann Oncol 2016;27:1110PD.
230. Gangadhar TC, Schneider BJ, Bauer TM, Wasser JS, Spira AI, et al. Efficacy and safety of epacadostat plus pembrolizumab treatment of NSCLC: preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol 2017;35:abstr9014.
231. Smith DC, Gajewski T, Hamid O, Wasser JS, Olszanski AJ, et al. Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol 2018;JCO2018789602.
232. Kakavand H, Wilmott JS, Menzies AM, Vilain R, Haydu LE, et al. PD-L1 expression and tumor-infiltrating lymphocytes define different subsets of MAPK inhibitor-treated melanoma patients. Clin Cancer Res 2015;21:3140-8.
233. Pfirschke C, Engblom C, Rickelt S, Cortez-Retamozo V, Garris C, et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity 2016;44:343-54.
234. Lin RL, Zhao LJ. Mechanistic basis and clinical relevance of the role of transforming growth factor-beta in cancer. Cancer Biol Med 2015;12:385-93.
236. Hanks BA, Holtzhausen A, Evans K, Heid M, Blobe GC. Combinatorial TGF-β signaling blockade and anti-CTLA-4 antibody immunotherapy in a murine BRAFV600E-PTEN-/-transgenic model of melanoma. Available from: https://ascopubs.org/doi/abs/10.1200/jco.2014.32.15_suppl.3011. [Last accessed on 21 Jun 2019].
237. Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ, et al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 2018;175:984-91.
238. Spiotto MT, Rowley DA, Schreiber H. Bystander elimination of antigen loss variants in established tumors. Nat Med 2004;10:294-8.
239. Van Willigne WW, Bloemendal M, Gerritsen WR, Schreibelt G, de Vries IJM, et al. Dendritic cell cancer therapy: vaccinating the right patient at the right time. Front Immunol 2018;9:2265.
240. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015;520:373-7.
241. Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immun 2015;36:265-76.
242. Emens LA. Cancer vaccines: on the threshold of success. Expert Opin Emerg Drugs 2008;13:295-308.