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Annual Review of Cancer Biology

Volume 6, 2022

Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

Abstract

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models,potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs.

Keyword(s): checkpoint inhibitors, immunoresistance, interferon-γ, JAK, major histocompatibility complex, tumor microenvironment
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2022-04-11
2025-02-17
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Literature Cited

  1. Acquavella N, Clever D, Yu Z, Roelke-Parker M, Palmer DC et al. 2015. Type I cytokines synergize with oncogene inhibition to induce tumor growth arrest. Cancer Immunol. Res. 3:37–47
     [Google Scholar]
  2. Ahmetlic F, Fauser J, Riedel T, Bauer V, Flessner C et al. 2021. Therapy of lymphoma by immune checkpoint inhibitors: the role of T cells, NK cells and cytokine-induced tumor senescence. J. Immunother. Cancer 9:e001660
     [Google Scholar]
  3. Al-Batran SE, Rafiyan MR, Atmaca A, Neumann A, Karbach J et al. 2005. Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma. Cancer Res 65:3937–41
     [Google Scholar]
  4. Alberts DS, Marth C, Alvarez RD, Johnson G, Bidzinski M et al. 2008. Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival. Gynecol. Oncol. 109:174–81
     [Google Scholar]
  5. Alspach E, Lussier DM, Schreiber RD. 2019. Interferon γ and its important roles in promoting and inhibiting spontaneous and therapeutic cancer immunity. Cold Spring Harb. Perspect. Biol. 11:3a028480
     [Google Scholar]
  6. Anderson DA 3rd, Dutertre CA, Ginhoux F, Murphy KM 2021. Genetic models of human and mouse dendritic cell development and function. Nat. Rev. Immunol. 21:101–15
     [Google Scholar]
  7. André P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J et al. 2018. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell 175:1731–43.e13
     [Google Scholar]
  8. Aptsiauri N, Ruiz-Cabello F, Garrido F. 2018. The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses. Curr. Opin. Immunol. 51:123–32
     [Google Scholar]
  9. Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A et al. 2017. IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Investig. 127:2930–40
     [Google Scholar]
  10. Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde N et al. 2014. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov 4:674–87
     [Google Scholar]
  11. Baruch EN, Wang J, Wargo JA 2021. Gut microbiota and antitumor immunity: potential mechanisms for clinical effect. Cancer Immunol. Res. 9:365–70
     [Google Scholar]
  12. Beck RJ, Slagter M, Beltman JB. 2019. Contact-dependent killing by cytotoxic T lymphocytes is insufficient for EL4 tumor regression in vivo. Cancer Res 79:3406–16
     [Google Scholar]
  13. Benci JL, Johnson LR, Choa R, Xu Y, Qiu J et al. 2019. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell 178:933–48.e14
     [Google Scholar]
  14. Benci JL, Xu B, Qiu Y, Wu TJ, Dada H et al. 2016. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell 167:1540–54.e12
     [Google Scholar]
  15. Bernal M, Ruiz-Cabello F, Concha A, Paschen A, Garrido F 2012. Implication of the β2-microglobulin gene in the generation of tumor escape phenotypes. Cancer Immunol. Immunother. 61:1359–71
     [Google Scholar]
  16. Braumüller H, Wieder T, Brenner E, Aßmann S, Hahn M et al. 2013. T-helper-1-cell cytokines drive cancer into senescence. Nature 494:361–65
     [Google Scholar]
  17. Brenner E, Schorg BF, Ahmetlic F, Wieder T, Hilke FJ et al. 2020. Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours. Nat. Commun. 11:1335
     [Google Scholar]
  18. Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A et al. 2019. An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell 36:385–401.e8
     [Google Scholar]
  19. Cachot A, Bilous M, Liu YC, Li X, Saillard M et al. 2021. Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer. Sci. Adv. 7:9eabe3348
     [Google Scholar]
  20. Chin YE, Kitagawa M, Kuida K, Flavell RA, Fu XY. 1997. Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis. Mol. Cell. Biol. 17:5328–37
     [Google Scholar]
  21. Chowell D, Krishna C, Pierini F, Makarov V, Rizvi NA et al. 2019. Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy. Nat. Med. 25:1715–20
     [Google Scholar]
  22. Chowell D, Morris LGT, Grigg CM, Weber JK, Samstein RM et al. 2018. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 359:582–87
     [Google Scholar]
  23. Cristescu R, Mogg R, Ayers M, Albright A, Murphy E et al. 2018. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 362:6411eaar3593
     [Google Scholar]
  24. Davoli T, Uno H, Wooten EC, Elledge SJ. 2017. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science 355:6322eaaf8399
     [Google Scholar]
  25. Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A et al. 2018. High response rate to PD-1 blockade in desmoplastic melanomas. Nature 553:347–50
     [Google Scholar]
  26. Ferris ST, Durai V, Wu R, Theisen DJ, Ward JP et al. 2020. cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity. Nature 584:624–29
     [Google Scholar]
  27. Gao J, Shi LZ, Zhao H, Chen J, Xiong L et al. 2016. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167:397–404.e9
     [Google Scholar]
  28. Garcia-Diaz A, Shin DS, Moreno BH, Saco J, Escuin-Ordinas H et al. 2017. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep 19:1189–201
     [Google Scholar]
  29. Germano G, Lu S, Rospo G, Lamba S, Rousseau B et al. 2021. CD4 T cell–dependent rejection of beta-2 microglobulin null mismatch repair–deficient tumors. Cancer Discov 11:1844–59
     [Google Scholar]
  30. Gettinger S, Choi J, Hastings K, Truini A, Datar I et al. 2017. Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung cancer. Cancer Discov 7:1420–35
     [Google Scholar]
  31. Gleave ME, Elhilali M, Fradet Y, Davis I, Venner P et al. 1998. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. N. Engl. J. Med 338:1265–71
     [Google Scholar]
  32. Gollob JA, Sciambi CJ, Huang Z, Dressman HK. 2005. Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-γ. Cancer Res 65:8869–77
     [Google Scholar]
  33. Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ et al. 2018. Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discov 8:730–49
     [Google Scholar]
  34. Grasso CS, Tsoi J, Onyshchenko M, Abril-Rodriguez G, Ross-Macdonald P et al. 2020. Conserved interferon-γ signaling drives clinical response to immune checkpoint blockade therapy in melanoma. Cancer Cell 38:500–15.e3
     [Google Scholar]
  35. Gulhan DC, Garcia E, Lee EK, Lindemann NI, Liu JF et al. 2020. Genomic determinants of de novo resistance to immune checkpoint blockade in mismatch repair–deficient endometrial cancer. JCO Precis. Oncol. 4:492–97
     [Google Scholar]
  36. Gurjao C, Liu D, Hofree M, AlDubayan SH, Wakiro I et al. 2019. Intrinsic resistance to immune checkpoint blockade in a mismatch repair–deficient colorectal cancer. Cancer Immunol. Res. 7:1230–36
     [Google Scholar]
  37. Hoekstra ME, Bornes L, Dijkgraaf FE, Philips D, Pardieck IN et al. 2020. Long-distance modulation of bystander tumor cells by CD8+ T cell-secreted IFNγ. Nat. Cancer 1:291–301
     [Google Scholar]
  38. Horn S, Leonardelli S, Sucker A, Schadendorf D, Griewank KG, Paschen A. 2018. Tumor CDKN2A-associated JAK2 loss and susceptibility to immunotherapy resistance. J. Natl. Cancer Inst. 110:677–81
     [Google Scholar]
  39. Ishizuka JJ, Manguso RT, Cheruiyot CK, Bi K, Panda A et al. 2019. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 565:43–48
     [Google Scholar]
  40. Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ et al. 2018. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 175:984–97.e24
     [Google Scholar]
  41. Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB et al. 2016. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat. Commun. 7:10582
     [Google Scholar]
  42. Kalaora S, Lee JS, Barnea E, Levy R, Greenberg P et al. 2020. Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma. Nat. Commun. 11:896
     [Google Scholar]
  43. Kalbasi A, Tariveranmoshabad M, Hakimi K, Kremer S, Campbell KM et al. 2020. Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Sci. Transl. Med. 12:565eabb0152
     [Google Scholar]
  44. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M et al. 1998. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. PNAS 95:7556–61
     [Google Scholar]
  45. Kearney CJ, Vervoort SJ, Hogg SJ, Ramsbottom KM, Freeman AJ et al. 2018. Tumor immune evasion arises through loss of TNF sensitivity. Sci. Immunol. 3:23eaar3451
     [Google Scholar]
  46. Kim YJ, Sheu KM, Tsoi J, Abril-Rodriguez G, Medina E et al. 2021. Melanoma dedifferentiation induced by IFN-γ epigenetic remodeling in response to anti-PD-1 therapy. J. Clin. Investig. 131:12e145859
     [Google Scholar]
  47. Kriegsman BA, Vangala P, Chen BJ, Meraner P, Brass AL et al. 2019. Frequent loss of IRF2 in cancers leads to immune evasion through decreased MHC class I antigen presentation and increased PD-L1 expression. J. Immunol. 203:1999–2010
     [Google Scholar]
  48. Lawson KA, Sousa CM, Zhang X, Kim E, Akthar R et al. 2020. Functional genomic landscape of cancer-intrinsic evasion of killing by T cells. Nature 586:120–26
     [Google Scholar]
  49. Lee JH, Shklovskaya E, Lim SY, Carlino MS, Menzies AM et al. 2020. Transcriptional downregulation of MHC class I and melanoma de-differentiation in resistance to PD-1 inhibition. Nat. Commun. 11:1897
     [Google Scholar]
  50. Liu D, Schilling B, Liu D, Sucker A, Livingstone E et al. 2019. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nat. Med. 25:1916–27
     [Google Scholar]
  51. Liu Y, Liang X, Yin X, Lv J, Tang K et al. 2017. Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells. Nat. Commun. 8:15207
     [Google Scholar]
  52. Luke JJ, Bao R, Sweis RF, Spranger S, Gajewski TF. 2019. WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clin. Cancer Res. 25:3074–83
     [Google Scholar]
  53. Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB et al. 2017. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547:413–18
     [Google Scholar]
  54. Márquez-Rodas I, Longo F, Rodriguez-Ruiz ME, Calles A, Ponce S et al. 2020. Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti–PD-1 for patients with anti-PD-1–refractory tumors. Sci. Transl. Med. 12:565eabb0391
     [Google Scholar]
  55. Matsushita H, Hosoi A, Ueha S, Abe J, Fujieda N et al. 2015. Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFNγ-dependent cell-cycle arrest. Cancer Immunol. Res. 3:26–36
     [Google Scholar]
  56. McGranahan N, Rosenthal R, Hiley CT, Rowan AJ, Watkins TBK et al. 2017. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171:1259–71.e11
     [Google Scholar]
  57. Middha S, Yaeger R, Shia J, Stadler ZK, King S et al. 2019. Majority of B2M-mutant and -deficient colorectal carcinomas achieve clinical benefit from immune checkpoint inhibitor therapy and are microsatellite instability-high. JCO Precis. Oncol. 3:1–14
     [Google Scholar]
  58. Mittal D, Gubin MM, Schreiber RD, Smyth MJ. 2014. New insights into cancer immunoediting and its three component phases–elimination, equilibrium and escape. Curr. Opin. Immunol. 27:16–25
     [Google Scholar]
  59. Montesion M, Murugesan K, Jin DX, Sharaf R, Sanchez N et al. 2021. Somatic HLA class I loss is a widespread mechanism of immune evasion which refines the use of tumor mutational burden as a biomarker of checkpoint inhibitor response. Cancer Discov 11:282–92
     [Google Scholar]
  60. Müller-Hermelink N, Braumüller H, Pichler B, Wieder T, Mailhammer R et al. 2008. TNFR1 signaling and IFN-γ signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13:507–18
     [Google Scholar]
  61. Muntasell A, Ochoa MC, Cordeiro L, Berraondo P, López-Díaz de Cerio A et al. 2017. Targeting NK-cell checkpoints for cancer immunotherapy. Curr. Opin. Immunol. 45:73–81
     [Google Scholar]
  62. Nagasaki J, Togashi Y, Sugawara T, Itami M, Yamauchi N et al. 2020. The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma. Blood Adv 4:4069–82
     [Google Scholar]
  63. Neubert NJ, Tille L, Barras D, Soneson C, Baumgaertner P et al. 2017. Broad and conserved immune regulation by genetically heterogeneous melanoma cells. Cancer Res 77:1623–36
     [Google Scholar]
  64. Nicolai CJ, Wolf N, Chang IC, Kirn G, Marcus A et al. 2020. NK cells mediate clearance of CD8+ T cell–resistant tumors in response to STING agonists. Sci. Immunol. 5:45eaaz2738
     [Google Scholar]
  65. Oh DY, Kwek SS, Raju SS, Li T, McCarthy E et al. 2020. Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer. Cell 181:1612–25.e13
     [Google Scholar]
  66. Oliveira G, Stromhaug K, Klaeger S, Kula T, Frederick DT et al. 2021. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 596:119–25
     [Google Scholar]
  67. Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay RE et al. 2018. A major chromatin regulator determines resistance of tumor cells to T cell–mediated killing. Science 359:770–75
     [Google Scholar]
  68. Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK et al. 2017. Identification of essential genes for cancer immunotherapy. Nature 548:537–42
     [Google Scholar]
  69. Perea F, Bernal M, Sánchez-Palencia A, Carretero J, Torres C et al. 2017. The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration. Int. J. Cancer 140:888–99
     [Google Scholar]
  70. Pérez-Ruiz E, Melero I, Kopecka J, Sarmento-Ribeiro AB, García-Aranda M, De Las Rivas J. 2020. Cancer immunotherapy resistance based on immune checkpoints inhibitors: targets, biomarkers, and remedies. Drug Resist. Updates 53:100718
     [Google Scholar]
  71. Pujade-Lauraine E, Guastalla JP, Colombo N, Devillier P, François E et al. 1996. Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy. J. Clin. Oncol. 14:343–50
     [Google Scholar]
  72. Rehwinkel J, Gack MU. 2020. RIG-I-like receptors: their regulation and roles in RNA sensing. Nat. Rev. Immunol. 20:537–51
     [Google Scholar]
  73. Ribas A, Medina T, Kirkwood JM, Zakharia Y, Gonzalez R et al. 2021. Overcoming PD-1 blockade resistance with CpG-A Toll-like receptor 9 agonist vidutolimod in patients with metastatic melanoma. Cancer Discov 11(12):5372998–3007
     [Google Scholar]
  74. Ribas A, Medina T, Kummar S, Amin A, Kalbasi A et al. 2018. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase Ib, multicenter study. Cancer Discov 8:1250–57
     [Google Scholar]
  75. Ribas A, Wolchok JD. 2018. Cancer immunotherapy using checkpoint blockade. Science 359:1350–55
     [Google Scholar]
  76. Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P et al. 2018. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J. Clin. Oncol. 36:633–41
     [Google Scholar]
  77. Rodig SJ, Gusenleitner D, Jackson DG, Gjini E, Giobbie-Hurder A et al. 2018. MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci. Transl. Med. 10:450eaar3342
     [Google Scholar]
  78. Roh W, Chen PL, Reuben A, Spencer CN, Prieto PA et al. 2017. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci. Transl. Med. 9:379eaah3560
     [Google Scholar]
  79. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. 2015. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160:48–61
     [Google Scholar]
  80. Rosenthal R, Cadieux EL, Salgado R, Bakir MA, Moore DA et al. 2019. Neoantigen-directed immune escape in lung cancer evolution. Nature 567:479–85
     [Google Scholar]
  81. Rouanne M, Zitvogel L, Marabelle A. 2020. Pegylated engineered IL2 plus anti-PD-1 monoclonal antibody: The nectar comes from the combination. Cancer Discov 10:1097–99
     [Google Scholar]
  82. Ruiz de Galarreta M, Bresnahan E, Molina-Sánchez P, Lindblad KE, Maier B et al. 2019. β-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov 9:1124–41
     [Google Scholar]
  83. Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M et al. 2017. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat. Commun. 8:1136
     [Google Scholar]
  84. Sánchez-Paulete AR, Cueto FJ, Martínez-López M, Labiano S, Morales-Kastresana A et al. 2016. Cancer immunotherapy with immunomodulatory anti-CD137 and anti–PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov 6:71–79
     [Google Scholar]
  85. Sánchez-Paulete AR, Teijeira A, Cueto FJ, Garasa S, Pérez-Gracia JL et al. 2017. Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy. Ann. Oncol. 28:xii44–55
     [Google Scholar]
  86. Sanderson NS, Puntel M, Kroeger KM, Bondale NS, Swerdlow M et al. 2012. Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells. PNAS 109:7835–40
     [Google Scholar]
  87. Schiller JH, Pugh M, Kirkwood JM, Karp D, Larson M, Borden E. 1996. Eastern Cooperative Group trial of interferon gamma in metastatic melanoma: an innovative study design. Clin. Cancer Res. 2:29–36
     [Google Scholar]
  88. Schrors B, Lubcke S, Lennerz V, Fatho M, Bicker A et al. 2017. HLA class I loss in metachronous metastases prevents continuous T cell recognition of mutated neoantigens in a human melanoma model. Oncotarget 8:28312–27
     [Google Scholar]
  89. Schumacher TN, Schreiber RD. 2015. Neoantigens in cancer immunotherapy. Science 348:69–74
     [Google Scholar]
  90. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. 2017. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168:707–23
     [Google Scholar]
  91. Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S et al. 2017. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov 7:188–201
     [Google Scholar]
  92. Spranger S, Bao R, Gajewski TF 2015. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 523:231–35
     [Google Scholar]
  93. Such L, Zhao F, Liu D, Thier B, Le-Trilling VTK et al. 2020. Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy. J. Clin. Investig. 130:4266–81
     [Google Scholar]
  94. Sucker A, Zhao F, Pieper N, Heeke C, Maltaner R et al. 2017. Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions. Nat. Commun. 8:15440
     [Google Scholar]
  95. Sucker A, Zhao F, Real B, Heeke C, Bielefeld N et al. 2014. Genetic evolution of T-cell resistance in the course of melanoma progression. Clin. Cancer Res. 20:6593–604
     [Google Scholar]
  96. Takeda K, Nakayama M, Hayakawa Y, Kojima Y, Ikeda H et al. 2017. IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting. Nat. Commun. 8:14607
     [Google Scholar]
  97. Taube JM, Klein A, Brahmer JR, Xu H, Pan X et al. 2014. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res. 20:5064–74
     [Google Scholar]
  98. Textor A, Schmidt K, Kloetzel PM, Weißbrich B, Perez C et al. 2016. Preventing tumor escape by targeting a post-proteasomal trimming independent epitope. J. Exp. Med. 213:2333–48
     [Google Scholar]
  99. Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K et al. 2011. NF-κB protects cells from gamma interferon-induced RIP1-dependent necroptosis. Mol. Cell. Biol. 31:2934–46
     [Google Scholar]
  100. Thibaut R, Bost P, Milo I, Cazaux M, Lemaître F et al. 2020. Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment. Nat. Cancer 1:302–14
     [Google Scholar]
  101. Torrejon DY, Abril-Rodriguez G, Champhekar AS, Tsoi J, Campbell KM et al. 2020. Overcoming genetically based resistance mechanisms to PD-1 blockade. Cancer Discov 10:1140–57
     [Google Scholar]
  102. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ et al. 2014. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–71
     [Google Scholar]
  103. Upadhyay R, Boiarsky JA, Pantsulaia G, Svensson-Arvelund J, Lin MJ et al. 2021. A critical role for Fas-mediated off-target tumor killing in T-cell immunotherapy. Cancer Discov 11:599–613
     [Google Scholar]
  104. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D et al. 2003. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 9:1269–74
     [Google Scholar]
  105. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C et al. 2015. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:207–11
     [Google Scholar]
  106. Von Hoff DD, Fleming TR, Macdonald JS, Goodman PJ, Van Damme J et al. 1990. Phase II evaluation of recombinant γ-interferon in patients with advanced pancreatic carcinoma: a Southwest Oncology Group study. J. Biol. Response Mod. 9:584–87
     [Google Scholar]
  107. Wang W, Green M, Choi JE, Gijon M, Kennedy PD et al. 2019. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569:270–74
     [Google Scholar]
  108. Wee ZN, Li Z, Lee PL, Lee ST, Lim YP, Yu Q. 2014. EZH2-mediated inactivation of IFN-γ-JAK-STAT1 signaling is an effective therapeutic target in MYC-driven prostate cancer. Cell Rep 8:204–16
     [Google Scholar]
  109. William WN Jr., Zhao X, Bianchi JJ, Lin HY, Cheng P et al. 2021. Immune evasion in HPV− head and neck precancer–cancer transition is driven by an aneuploid switch involving chromosome 9p loss. PNAS 118:19e2022655118
     [Google Scholar]
  110. Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C et al. 2000. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br. J. Cancer 82:1138–44
     [Google Scholar]
  111. Woo S-R, Fuertes MB, Corrales L, Spranger S, Furdyna MJ et al. 2014. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:830–42
     [Google Scholar]
  112. Wrangle JM, Velcheti V, Patel MR, Garrett-Mayer E, Hill EG et al. 2018. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol 19:694–704
     [Google Scholar]
  113. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W et al. 2016. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375:819–29
     [Google Scholar]
  114. Zhao F, Sucker A, Horn S, Heeke C, Bielefeld N et al. 2016. Melanoma lesions independently acquire T-cell resistance during metastatic latency. Cancer Res 76:4347–58
     [Google Scholar]
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Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade
Annual Review of Cancer Biology 6, 85 (2022); https://doi.org/10.1146/annurev-cancerbio-070220-111016
/content/journals/10.1146/annurev-cancerbio-070220-111016
/content/journals/10.1146/annurev-cancerbio-070220-111016
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  • Article Type: Review Article

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