REFERENCES

1. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol 2011;29:235-71.

2. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 2000;356:1795-9.

3. Corrales L, Matson V, Flood B, Spranger S, Gajewski TF. Innate immune signaling and regulation in cancer immunotherapy. Cell Res 2017;27:96-108.

4. Bonavida B, Chouaib S. Resistance to anticancer immunity in cancer patients: potential strategies to reverse resistance. Ann Oncol 2017;28:457-67.

5. Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Valsesia-Wittmann S, et al. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol 2019;10:168.

6. Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 2005;5:296-306.

7. Ueno H, Schmitt N, Palucka AK, Banchereau J. Dendritic cells and humoral immunity in humans. Immunol Cell Biol 2010;88:376-80.

8. Gardner A, Ruffell B. Dendritic cells and cancer immunity. Trends Immunol 2016;37:855-65.

9. Zelenay S, Reis e Sousa C. Adaptive immunity after cell death. Trends Immunol 2013;34:329-35.

10. Schreibelt G, Tel J, Sliepen KH, Benitez-Ribas D, Figdor CG, et al. Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy. Cancer Immunol Immunother 2010;59:1573-82.

11. Liu Y, Zeng G. Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J Immunother 2012;35:299-308.

12. Fang H, Ang B, Xu X, Huang X, Wu Y, et al. TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells. Cell Mol Immunol 2014;11:150-9.

13. Krasnova Y, Putz EM, Smyth MJ, Souza-Fonseca-Guimaraes F. Bench to bedside: NK cells and control of metastasis. Clin Immunol 2017;177:50-9.

14. Artis D, Spits H. The biology of innate lymphoid cells. Nature 2015;517:293-301.

15. Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer 2016;16:7-19.

16. Pahl J, Cerwenka A. Tricking the balance: NK cells in anti-cancer immunity. Immunobiology 2017;222:11-20.

17. Wang W, Erbe AK, Hank JA, Morris ZS, Sondel PM. NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Front Immunol 2015;6:68.

18. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, et al. Innate or adaptive immunity? The example of natural killer cells. Science 2011;331:44-9.

19. Stangl S, Tontcheva N, Sievert W, Shevtsov M, Niu M, et al. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Gro. Int J Cancer 2018;142:1911-25.

20. Hoshikawa M, Aoki T, Matsushita H, Karasaki T, Hosoi A, et al. NK cell and IFN signatures are positive prognostic biomarkers for resectable pancreatic cancer. Biochem Biophys Res Commun 2018;495:2058-65.

21. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41:14-20.

22. DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol 2019;19:369-82.

23. Zhang M, He Y, Sun X, Li Q, Wang W, et al. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res 2014;7:1-16.

24. Yuan A, Hsiao YJ, Chen HY, Chen HW, Ho CC, et al. Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression. Sci Rep 2015;5:14273.

25. Emens LA, Ascierto PA, Darcy PK, Demaria S, Eggermont AMM, et al. Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer 2017;81:116-29.

26. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science 2011;331:1565-70.

27. Radvanyi LG, Mills GB, Vaziri H, Miller RG, Shi Y, et al. CD28 costimulation inhibits TCR-induced apoptosis during a primary T cell response. J Immunol 1996;156:1788-98.

28. Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 2005;54:721-8.

29. Haabeth OAW, Bogen B, Corthay A. A model for cancer-suppressive inflammation. Oncoimmunology 2012;1:1146-55.

30. Burkholder B, Huang RY, Burgess R, Luo S, Jones VS, et al. Tumor-induced perturbations of cytokines and immune cell networks. Biochim Biophys Acta 2014;1845:182-201.

31. Martínez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res 2015;21:5047-56.

32. Lawand M, Déchanet-Merville J, Dieu-Nosjean MC. Key features of gamma-delta T-cell subsets in human diseases and their immunotherapeutic implications. Front Immunol 2017;8:761.

33. Zoine JT, Knight KA, Fleischer LC, Sutton KS, Goldsmith KC, et al. Ex vivo expanded patient-derived γδ T-cell immunotherapy enhances neuroblastoma tumor regression in a murine model. Oncoimmunology 2019;8:1593804.

34. Muto M, Baghdadi M, Maekawa R, Wada H, Seino KI. Myeloid molecular characteristics of human γ δ T cells support their acquisition of tumor antigen-presenting capacity. Cancer Immunol Immunother 2015;64:941-9.

35. Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human gammadelta T Cells. Science 2005;309:264-8.

36. Tsou P, Katayama H, Ostrin EJ, Hanash SM. The emerging role of B cells in tumor immunity. Cancer Res 2016;76:5597-601.

37. Kimiz-Gebologlu I, Gulce-Iz S, Biray-Avci C. Monoclonal antibodies in cancer immunotherapy. Mol Biol Rep 2018;45:2935-40.

38. McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 2017;168:613-28.

39. Jamal-Hanjani M, Quezada SA, Larkin J, Swanton C. Translational implications of tumor heterogeneity. Clin Cancer Res 2015;21:1258-66.

40. Hölzel M, Bovier A, Tüting T. Plasticity of tumour and immune cells: a source of heterogeneity and a cause for therapy resistance? Nat Rev Cancer 2013;13:365-76.

41. Disis ML. Immune regulation of cancer. J Clin Oncol 2010;28:4531-8.

42. Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature 2012;490:412-6.

43. 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.

44. Watkins TBK, Schwarz RF. Phylogenetic quantification of intratumor heterogeneity. Cold Spring Harb Perspect Med 2018;8:pii: a028316.

45. Connor ME, Stern PL. Loss of MHC class-I expression in cervical carcinomas. Int J Cancer 1990;46:1029-34.

46. Jäger 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.

47. Khong HT, Wang QJ, Rosenberg SA. Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: Tumor escape by antigen loss and loss of MHC expression. J Immunother 2004;27:184-90.

48. Verdegaal EME, De Miranda NFCC, Visser M, Harryvan T, Van Buuren MM, et al. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature 2016;536:91-5.

49. Aptsiauri N, Ruiz-Cabello F, Garrido F. The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses. Curr Opin Immunol 2018;51:123-32.

50. Qian J, Luo F, Yang J, Liu J, Liu R, et al. TLR2 promotes glioma immune evasion by downregulating MHC class II molecules in microglia. Cancer Immunol Res 2018;6:1220-33.

51. Rimsza LM, Roberts RA, Miller TP, Unger JM, LeBlanc M, et al. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular. Blood 2004;103:4251-8.

52. Cabrera CM, Jiménez P, Cabrera T, Esparza C, Ruiz-Cabello F, et al. Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways: β2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors. Tissue Antigens 2003;61:211-9.

53. Vlková V, Štěpánek I, Hrušková V, Šenigl F, Šrámek M, et al. Epigenetic regulations in the IFNγ signalling pathway : IFNγ- mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes. Oncotarget 2014;5:6923-35.

54. Schmiedel D, Mandelboim O. NKG2D ligands-critical targets for cancer immune escape and therapy. Front Immunol 2018;9:2040.

55. Ghadially H, Brown L, Lloyd C, Lewis L, Lewis A, et al. MHC class i chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue. Br J Cancer 2017;116:1208-17.

56. Fernández-Messina L, Reyburn HT, Valés-Gómez M. A short half-life of ULBP1 at the cell surface due to internalization and proteosomal degradation. Immunol Cell Biol 2016;94:479-85.

57. Raneros AB, Puras AM, Colado E, Bernal Del Castillo T, Mogorron AV, et al. Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition. Oncotarget 2017;8:31959-76.

58. Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CNJ, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res 2010;70:5213-9.

59. Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res 2013;19:1225-31.

60. 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.

61. Li B, Zhang J, Su Y, Hou Y, Wang Z, et al. Overexpression of PTEN may increase the effect of pemetrexed on A549 cells via inhibition of the PI3K/AKT/mTOR pathway and carbohydrate metabolism. Mol Med Rep 2019;20:3793-801.

62. Singh S, Apata T, Gordetsky J, Singh R. Docetaxel combined with thymoquinone induces apoptosis in prostate cancer cells via inhibition of the PI3K/AKT signaling pathway. Cancers (Basel) 2019;11:E1390.

63. Reed JC. Bcl-2 on the brink of breakthroughs in cancer treatment. Cell Death Differ 2018;25:3-6.

64. Marques CA, Hähnel PS, Wölfel C, Thaler S, Huber C, et al. An immune escape screen reveals Cdc42 as regulator of cancer susceptibility to lymphocyte-mediated tumor suppression. Blood 2008;111:1413-9.

65. Maruyama R, Yamana K, Itoi T, Hara N, Bilim V, et al. Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma. Br J Cancer 2006;95:1244-9.

66. Delbridge ARD, Grabow S, Strasser A, Vaux DL. Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. Nat Rev Cancer 2016;16:99-109.

67. Fanger NA, Maliszewski CR, Schooley K, Griffith TS. Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med 1999;190:1155-64.

68. Griffith TS, Wiley SR, Kubin MZ, Sedger LM, Maliszewski CR, et al. Monocyte-mediated tumoricidal activity via the tumor necrosis factor- related cytokine, TRAIL. J Exp Med 1999;189:1343-54.

69. Day TW, Huang S, Safa AR. c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells. Biochem Pharmacol 2008;76:1694-704.

70. Engelsgjerd S, Kunnimalaiyaan S, Kandil E, Gamblin TC, Kunnimalaiyaan M. Xanthohumol increases death receptor 5 expression and enhances apoptosis with the TNF-related apoptosis-inducing ligand in neuroblastoma cell lines. PLoS One 2019;14:e0213776.

71. Baritaki S, Huerta-Yepez S, Sakai T, Spandidos DA, Bonavida B. Chemotherapeutic drugs sensitize cancer cells to TRAIL-mediated apoptosis: up-regulation of DR5 and inhibition of Yin Yang 1. Mol Cancer Ther 2007;6:1387-99.

72. Huerta-Yepez S, Vega M, Escoto-Chavez SE, Murdock B, Sakai T, et al. Nitric oxide sensitizes tumor cells to TRAIL-induced apoptosis via inhibition of the DR5 transcription repressor Yin Yang 1. Nitric Oxide 2009;20:39-52.

73. Zang F, Wei X, Leng X, Yu M, Sun B. C-FLIP(L) contributes to TRAIL resistance in HER2-positive breast cancer. Biochem Biophys Res Commun 2014;450:267-73.

74. Golks A, Brenner D, Krammer PH, Lavrik IN. The c-FLIP-NH2 terminus (p22-FLIP) induces NF-κB activation. J Exp Med 2006;203:1295-305.

75. Bardhan K, Anagnostou T, Boussiotis VA. The PD1: PD-L1/2 pathway from discovery to clinical implementation. Front Immunol 2016;7:550.

76. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64.

77. Arasanz H, Gato-Cañas M, Zuazo M, Ibañez-Vea M, Breckpot K, et al. PD1 signal transduction pathways in T cells. Oncotarget 2017;8:51936-45.

78. Hays E, Bonavida B. YY1 regulates cancer cell immune resistance by modulating PD-L1 expression. Drug Resist Updat 2019;43:10-28.

79. Zhang J, Bu X, Wang H, Zhu Y, Geng Y, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 2018;553:91-5.

80. Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther 2016;9:5023-39.

81. Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev 2009;229:12-26.

82. Mead KI, Zheng Y, Manzotti CN, Perry LCA, Liu MKP, et al. Exocytosis of CTLA-4 is dependent on phospholipase D and ADP ribosylation factor-1 and stimulated during activation of regulatory T cells. J Immunol 2005;174:4803-11.

83. Valk E, Leung R, Kang H, Kaneko K, Rudd CE, et al. T cell receptor-interacting molecule acts as a chaperone to modulate surface expression of the CTLA-4 coreceptor. Immunity 2006;25:807-21.

84. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994;1:793-801.

85. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 2011;332:600-3.

86. Chen X, Shao Q, Hao S, Zhao Z, Wang Y, et al. CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function. Oncotarget 2017;8:13703-15.

87. Bengsch F, Knoblock DM, Liu A, McAllister F, Beatty GL. CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer. Cancer Immunol Immunother 2017;66:1609-17.

88. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;133:571-3.

89. Wu M, Chen X, Lou J, Zhang S, Zhang X, et al. TGF-β1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment. Oncotarget 2016;7:44534-44.

90. Zhang S, Ke X, Zeng S, Wu M, Lou J, et al. Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment. Cell Mol Immunol 2015;12:580-91.

91. Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2001;2:301-6.

92. Whiteside TL. FOXP3+ Treg as a therapeutic target for promoting anti-tumor immunity. Expert Opin Ther Targets 2018;22:353-63.

93. Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, et al. Two FOXP3 + CD4 + T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med 2016;22:679-84.

94. Strauss L, Bergmann C, Whiteside TL. Human circulating CD4 + CD25 high Foxp3 + regulatory T cells kill autologous CD8 + but not CD4 + responder cells by Fas-mediated apoptosis. J Immunol 2009;182:1469-80.

95. Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res 2017;27:109-18.

96. Cao X, Cai SF, Fehniger TA, Song J, Collins LI, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007;27:635-46.

97. Li K, Chen F, Xie H. Decreased FOXP3+ and GARP+ tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer. Onco Targets Ther 2016;9:3525-33.

98. 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.

99. Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol 2016;37:208-20.

100. Liu Y, Lai L, Chen Q, Song Y, Xu S, et al. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol 2012;188:5500-10.

101. Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009;182:4499-506.

102. Ku AW, Muhitch JB, Powers CA, Diehl M, Kim M, et al. Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes. Elife 2016;5:e17375.

103. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.

104. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007;179:977-83.

105. Chen Q, Zhang XHF, Massagué J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 2011;20:538-49.

106. Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, et al. L-arginine modulates t cell metabolism and enhances survival and anti-tumor activity. Cell 2016;167:829-42.

107. 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.

108. Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CMT, et al. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 2014;26:623-37.

109. 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.

110. Lin H, Wei S, Hurt EM, Green MD, Zhao L, et al. Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. J Clin Invest 2018;128:805-15.

111. Smith AL, Robin TP, Ford HL. Molecular pathways: targeting the TGF-β pathway for cancer therapy. Clin Cancer Res 2012;18:4514-21.

112. Liu VC, Wong LY, Jang T, Shah AH, Park I, et al. Tumor evasion of the immune system by converting CD4 + CD25 - T cells into CD4 + CD25 + T regulatory cells: role of tumor-derived TGF-β. J Immunol 2007;178:2883-92.

113. Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, et al. Transforming growth factor-β induces development of the T H17 lineage. Nature 2006;441:231-4.

114. 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.

115. 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.

116. Ito S ei, Shirota H, Kasahara Y, Saijo K, Ishioka C. IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model. Cancer Immunol Immunother 2017;66:1485-96.

117. Lamichhane P, Karyampudi L, Shreeder B, Krempski J, Bahr D, et al. IL10 release upon PD-1 blockade sustains immunosuppression in ovarian cancer. Cancer Res 2017;77:6667-78.

118. Fabre J, Giustiniani J, Garbar C, Antonicelli F, Merrouche Y, et al. Targeting the tumor microenvironment: the protumor effects of IL-17 related to cancer type. Int J Mol Sci 2016;17:1433.

119. Junttila MR, De Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013;501:346-54.

120. Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 2011;208:1949-62.

121. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008;14:518-27.

122. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T reg cells. Nature 2011;475:226-30.

123. Osada T, Chong G, Tansik R, Hong T, Spector N, et al. The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer Immunol Immunother 2008;57:1115-24.

124. Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res 2012;72:2746-56.

125. Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells. Immunol Rev 2003;193:70-81.

126. Chhabra A, Mukherji B, Batra D. Activation induced cell death (AICD) of human melanoma antigen-specific TCR engineered CD8 T cells involves JNK, Bim and p53. Expert Opin Ther Targets 2017;21:117-29.

127. Scheffel MJ, Scurti G, Simms P, Garrett-Mayer E, Mehrotra S, et al. Efficacy of adoptive T-cell therapy isimproved by treatment with the antioxidant N-acetyl cysteine, which limits activation-induced T-cell death. Cancer Res 2016;70:6006-16.

128. Schulte M, Reiss K, Lettau M, Maretzky T, Ludwig A, et al. ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. Cell Death Differ 2007;14:1040-9.

129. Chhabra A. Mitochondria-centric activation induced cell death of cytolytic T lymphocytes and its implications for cancer immunotherapy. Vaccine 2010;28.

130. Huang D, Chen J, Yang L, Ouyang Q, Li J, et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat Immunol 2018;19:1112-25.

131. Firor AE, Jares A, Ma Y. From humble beginnings to success in the clinic: chimeric antigen receptor-modified T-cells and implications for immunotherapy. Exp Biol Med 2015;240:1087-98.

132. June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018;359:1361-5.

133. Wang J, Hu Y, Huang H. Current development of chimeric antigen receptor T-cell therapy. Stem Cell Investig 2018;5:44.

134. Wang Z, Wu Z, Liu Y, Han W. New development in CAR-T cell therapy. J Hematol Oncol 2017;10:53.

135. Staff N. With FDA approval for advanced lymphoma, second CAR T-cell therapy moves to the clinic. Natl Cancer Inst 2017. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2017/yescarta-fda-lymphoma [Last accessed on 25 Dec 2019].

136. Yan Z, Cao J, Cheng H, Qiao J, Zhang H, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol 2019;6:e521-9.

137. Martinez M, Moon EK. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front Immunol 2019;10:128.

138. Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, et al. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 2016;164:780-91.

139. Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med 2015;21:24-33.

140. D’Angelo SP. Manipulating the immune system with checkpoint inhibitors for patients with metastatic sarcoma. Am Soc Clin Oncol Educ B 2016;36:e558-64.

141. Bennani-Baiti N, Thanarajasingam G, Ansell S. Checkpoint inhibitors for the treatment of hodgkin lymphoma. Expert Rev Clin Immunol 2016;12:673-9.

142. Chuang J, Chao J, Hendifar A, Klempner SJ, Gong J. Checkpoint inhibition in advanced gastroesophageal cancer: clinical trial data, molecular subtyping, predictive biomarkers, and the potential of combination therapies. Transl Gastroenterol Hepatol 2019;4:63.

143. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 2015;372:311-9.

144. Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017;377:1824-35.

145. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, et al. Combined nivolumab and ipilimumab or monotherapy in untreated Melanoma. N Engl J Med 2015;373:23-34.

146. Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open 2017;2:e000213.

147. Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015;162:1229-41.

148. O’Donnell JS, Long G V, Scolyer RA, Teng MWL, Smyth MJ. Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev 2017;52:71-81.

149. Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 2016;17:e542-51.

150. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.

151. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-20.

152. Francis DM, Thomas SN. Progress and opportunities for enhancing the delivery and efficacy of checkpoint inhibitors for cancer immunotherapy. Adv Drug Deliv Rev 2017;114:33-42.

153. Gordon S, Akopyan G, Garban H, Bonavida B. Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 2006;25:1125-42.

154. Bonavida B, Jazirehi AR, Vega MI, Huerta-Yepez S, Baritaki S. Roles each of Snail, Yin Yang 1, and RKIP in the regulation of tumor cells chemo- immuno-resistance to apoptosis. For Immunopathol Dis Therap 2013;4:79-92.

155. Rathore R, McCallum JE, Varghese E, Florea AM, Büsselberg D. Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs). Apoptosis 2017;22:898-919.

156. Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol 2015;35:S78-103.

157. Ma L, Han M, Keyoumu Z, Wang H, Keyoumu S. Immunotherapy of dual-function vector with both immunostimulatory and B-cell lymphoma 2 (Bcl-2)-silencing effects on gastric carcinoma. Med Sci Monit 2017;23:1980-91.

158. Soragni A, Janzen DM, Johnson LM, Lindgren AG, Thai-Quynh Nguyen A, et al. A designed inhibitor of p53 aggregation rescues p53 tumor suppression in ovarian carcinomas. Cancer Cell 2016;29:90-103.

159. Baritaki S, Militello L, Malaponte G, Spandidos DA, Salcedo M, et al. The anti-CD20 mAb LFB-R603 interrupts the dysregulated NF-κB/Snail/ RKIP/PTEN resistance loop in B-NHL cells: role in sensitization to TRAIL apoptosis. Int J Oncol 2011;38:1683-94.

160. Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, et al. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol 2016;27:1482-92.

161. Nakamura K, Smyth MJ. Targeting cancer-related inflammation in the era of immunotherapy. Immunol Cell Biol 2017;95:325-32.

162. Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, et al. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest 2013;123:2447-63.

163. Taylor NA, Vick SC, Iglesia MD, Brickey WJ, Midkiff BR, et al. Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer. J Clin Invest 2017;127:3472-83.

164. Dominguez GA, Condamine T, Mony S, Hashimoto A, Wang F, et al. Selective targeting of myeloid-derived suppressor cells in cancer patients using DS-8273a, an agonistic TRAIL-R2 antibody. Clin Cancer Res 2017;23:2942-50.

165. Georgoudaki AM, Prokopec KE, Boura VF, Hellqvist E, Sohn S, et al. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep 2016;15:2000-11.

166. Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliv Rev 2017;114.

167. Yang L, Achreja A, Yeung TL, Mangala LS, Jiang D, et al. Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth. Cell Metab 2016;24:685-700.

168. Lin Z, Zhang Q, Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: challenges and future directions. Eur J Pharmacol 2016;793:76-81.

169. Hatfield SM, Kjaergaard J, Lukashev D, Schreiber TH, Belikoff B, et al. Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med 2015;7:277ra30.

170. Kim JY, Lee JY. Targeting tumor adaption to chronic hypoxia: implications for drug resistance, and how it can be overcome. Int J Mol Sci 2017;18:1854.

171. Fu J, Malm IJ, Kadayakkara DK, Levitsky H, Pardoll D, et al. Preclinical evidence that PD1 blockade cooperates with cancer vaccine TEGVAX to elicit regression of established tumors. Cancer Res 2014;74:4042-52.

172. Chen L, Douglass J, Kleinberg L, Ye X, Marciscano AE, et al. Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys 2018;100:916-25.

173. Lu X, Horner JW, Paul E, Shang X, Troncoso P, et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 2017;543:728-32.

174. Pallasch CP, Leskov I, Braun CJ, Vorholt D, Drake A, et al. Sensitizing protective tumor microenvironments to antibody-mediated therapy. Cell 2014;156:590-602.

175. Cao K, Wang G, Li W, Zhang L, Wang R, et al. Histone deacetylase inhibitors prevent activation-induced cell death and promote anti-tumor immunity. Oncogene 2015;34:5960-70.

176. Nixon NA, Blais N, Ernst S, Kollmannsberger C, Bebb G, et al. Current landscape of immunotherapy in the treatment of solid tumours, with future opportunities and challenges. Curr Oncol 2018;25:e373-84.

177. Tahmasebi S, Elahi R, Esmaeilzadeh A. Solid tumors challenges and new insights of car t cell engineering. Stem Cell Rev Reports 2019;15:619-36.

178. Bol KF, Schreibelt G, Gerritsen WR, De Vries IJM, Figdor CG. Dendritic cell-based immunotherapy: state of the art and beyond. Clin Cancer Res 2016;22:1897-906.

179. Ardolino M, Azimi CS, Iannello A, Trevino TN, Horan L, et al. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. J Clin Invest 2014;124:4781-94.

180. Natural killer cells for cancer immunotherapy: a new CAR is catching up. EBioMedicine 2019;39:1-2.

181. Vivarelli S, Salemi R, Candido S, Falzone L, Santagati M, et al. Gut microbiota and cancer: from pathogenesis to therapy. Cancers (Basel) 2019;11:38.

182. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018;359:97-103.

183. Hanauer D, Rhodes D, Sinha-Kumar C, Chinnaiyan A. Bioinformatics approaches in the study of cancer. Curr Mol Med 2007;7:133-41.

184. Trebeschi S, Drago SG, Birkbak NJ, Kurilova I, Cǎlin AM, et al. Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers. Ann Oncol 2019;30:998-1004.

Cancer Drug Resistance
ISSN 2578-532X (Online)

Portico

All published articles will preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles will preserved here permanently:

https://www.portico.org/publishers/oae/