IMMUNE NETWORK

  • 제20권1호
  • /
  • Pages.6.1-6.20
  • /
  • 2020
  • /
  • 1598-2629(pISSN)
  • /
  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지
DOI QR코드

DOI QR Code

IL-17-Producing Cells in Tumor Immunity: Friends or Foes?

  • Da-Sol Kuen (Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Byung-Seok Kim (Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Yeonseok Chung (Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University)
  • 투고 : 2019.12.29
  • 심사 : 2020.01.26
  • 발행 : 2020.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8+ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

키워드

과제정보

This work was supported by the research grant (2017R1A2B3007392; to YC), the Basic Science Research Program (2016R1A6A3A11933284; to Kim BS), and the Global Ph.D. Fellowship Program (2017H1A2A1042662; to Kuen DS) from the National Research Foundation of Korea (NRF) funded by the Ministry of Education of Korea.

참고문헌

  1. Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, Cosmi L, Lunardi C, Annunziato F, Romagnani S, et al. Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 2010;115:335-343. https://doi.org/10.1182/blood-2009-04-216085
  2. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT. Transforming growth factor-β induces development of the TH17 lineage. Nature 2006;441:231-234. https://doi.org/10.1038/nature04754
  3. Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 2009;30:576-587. https://doi.org/10.1016/j.immuni.2009.02.007
  4. McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O'Shea JJ, Cua DJ. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 2009;10:314-324. https://doi.org/10.1038/ni.1698
  5. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126:1121-1133. https://doi.org/10.1016/j.cell.2006.07.035
  6. Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C. Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 2006;16:902-907. https://doi.org/10.1038/sj.cr.7310106
  7. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, et al. Regulation of inflammatory responses by IL-17F. J Exp Med 2008;205:1063-1075. https://doi.org/10.1084/jem.20071978
  8. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011;12:568-575. https://doi.org/10.1038/ni.2031
  9. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, Suter T, Becher B. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12:560-567. https://doi.org/10.1038/ni.2027
  10. Kim BS, Park YJ, Chung Y. Targeting IL-17 in autoimmunity and inflammation. Arch Pharm Res 2016;39:1537-1547. https://doi.org/10.1007/s12272-016-0823-8
  11. Zhong W, Li Q. Rituximab or irradiation promotes IL-17 secretion and thereby induces resistance to rituximab or irradiation. Cell Mol Immunol 2017;14:1020-1022. https://doi.org/10.1038/cmi.2017.124
  12. Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A, Paulos CM, Palmer DC, Touloukian CE, Ptak K, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008;112:362-373.
  13. Kryczek I, Wei S, Szeliga W, Vatan L, Zou W. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 2009;114:357-359.
  14. Sethi V, Kurtom S, Tarique M, Lavania S, Malchiodi Z, Hellmund L, Zhang L, Sharma U, Giri B, Garg B, et al. Gut microbiota promotes tumor growth in mice by modulating immune response. Gastroenterology 2018;155:33-37.e6. https://doi.org/10.1053/j.gastro.2018.04.001
  15. Kuang DM, Peng C, Zhao Q, Wu Y, Zhu LY, Wang J, Yin XY, Li L, Zheng L. Tumor-activated monocytes promote expansion of IL-17-producing CD8+ T cells in hepatocellular carcinoma patients. J Immunol 2010;185:1544-1549. https://doi.org/10.4049/jimmunol.0904094
  16. Du JW, Xu KY, Fang LY, Qi XL. Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer. Mol Med Rep 2012;6:1099-1102. https://doi.org/10.3892/mmr.2012.1036
  17. Irshad S, Flores-Borja F, Lawler K, Monypenny J, Evans R, Male V, Gordon P, Cheung A, Gazinska P, Noor F, et al. RORγt+ Innate Lymphoid Cells Promote Lymph Node Metastasis of Breast Cancers. Cancer Res 2017;77:1083-1096.
  18. Rei M, Goncalves-Sousa N, Lanca T, Thompson RG, Mensurado S, Balkwill FR, Kulbe H, Pennington DJ, Silva-Santos B. Murine CD27(-) Vγ6(+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages. Proc Natl Acad Sci U S A 2014;111:E3562-E3570.
  19. Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, et al. The tumor-promoting actions of TNF-α involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest 2009;119:3011-3023. https://doi.org/10.1172/JCI39065
  20. Cheng M, Qian L, Shen G, Bian G, Xu T, Xu W, Shen G, Hu S. Microbiota modulate tumoral immune surveillance in lung through a γδT17 immune cell-dependent mechanism. Cancer Res 2014;74:4030-4041.
  21. Calcinotto A, Brevi A, Chesi M, Ferrarese R, Garcia Perez L, Grioni M, Kumar S, Garbitt VM, Sharik ME, Henderson KJ, et al. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun 2018;9:4832.
  22. Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 2015;522:345-348. https://doi.org/10.1038/nature14282
  23. Chang SH, Mirabolfathinejad SG, Katta H, Cumpian AM, Gong L, Caetano MS, Moghaddam SJ, Dong C. T helper 17 cells play a critical pathogenic role in lung cancer. Proc Natl Acad Sci U S A 2014;111:5664-5669. https://doi.org/10.1073/pnas.1319051111
  24. Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A, Hu B, Ameh S, Sandel D, Liang XS, Mazzilli S, et al. Commensal microbiota promote lung cancer development via γδ T cells. Cell 2019;176:998-1013.e16. https://doi.org/10.1016/j.cell.2018.12.040
  25. You R, DeMayo FJ, Liu J, Cho SN, Burt BM, Creighton CJ, Casal RF, Lazarus DR, Lu W, Tung HY, et al. IL17A regulates tumor latency and metastasis in lung adeno and squamous SQ.2b and AD.1 cancer. Cancer Immunol Res 2018;6:645-657. https://doi.org/10.1158/2326-6066.CIR-17-0554
  26. Wang L, Yi T, Zhang W, Pardoll DM, Yu H. IL-17 enhances tumor development in carcinogen-induced skin cancer. Cancer Res 2010;70:10112-10120. https://doi.org/10.1158/0008-5472.CAN-10-0775
  27. Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J, DiGiovanni J. Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest 2004;114:720-728. https://doi.org/10.1172/JCI200421032
  28. Housseau F, Wu S, Wick EC, Fan H, Wu X, Llosa NJ, Smith KN, Tam A, Ganguly S, Wanyiri JW, et al. Redundant innate and adaptive sources of IL17 production drive colon tumorigenesis. Cancer Res 2016;76:2115-2124.
  29. Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E, Vatan L, Szeliga W, Dou Y, Owens S, et al. IL-22+CD4+ T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity 2014;40:772-784. https://doi.org/10.1016/j.immuni.2014.03.010
  30. Wang K, Kim MK, Di Caro G, Wong J, Shalapour S, Wan J, Zhang W, Zhong Z, Sanchez-Lopez E, Wu LW, et al. Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity 2014;41:1052-1063. https://doi.org/10.1016/j.immuni.2014.11.009
  31. Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, Szabady RL, Harrison O, Powrie F. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med 2013;210:917-931. https://doi.org/10.1084/jem.20122308
  32. Abousamra NK, Salah El-Din M, Helal R. Prognostic value of Th17 cells in acute leukemia. Med Oncol 2013;30:732.
  33. Han Y, Ye A, Bi L, Wu J, Yu K, Zhang S. Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia. Cancer Sci 2014;105:933-942. https://doi.org/10.1111/cas.12459
  34. Chen WC, Lai YH, Chen HY, Guo HR, Su IJ, Chen HH. Interleukin-17-producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor. Histopathology 2013;63:225-233. https://doi.org/10.1111/his.12156
  35. Faucheux L, Grandclaudon M, Perrot-Dockes M, Sirven P, Berger F, Hamy AS, Fourchotte V, Vincent-Salomon A, Mechta-Grigoriou F, Reyal F, et al. A multivariate Th17 metagene for prognostic stratification in T cell non-inflamed triple negative breast cancer. OncoImmunology 2019;8:e1624130.
  36. Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, Lin Z, Zhu B. IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun 2011;407:348-354. https://doi.org/10.1016/j.bbrc.2011.03.021
  37. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 2011;71:1263-1271. https://doi.org/10.1158/0008-5472.CAN-10-2907
  38. Chen J, Chen Z. The effect of immune microenvironment on the progression and prognosis of colorectal cancer. Med Oncol 2014;31:82.
  39. Alves JJ, De Medeiros Fernandes TA, De Araujo JM, Cobucci RN, Lanza DC, Bezerra FL, Andrade VS, Fernandes JV. Th17 response in patients with cervical cancer. Oncol Lett 2018;16:6215-6227.
  40. Punt S, Fleuren GJ, Kritikou E, Lubberts E, Trimbos JB, Jordanova ES, Gorter A. Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer. Oncoimmunology 2015;4:e984539.
  41. Wang B, Li L, Liao Y, Li J, Yu X, Zhang Y, Xu J, Rao H, Chen S, Zhang L, et al. Mast cells expressing interleukin 17 in the muscularis propria predict a favorable prognosis in esophageal squamous cell carcinoma. Cancer Immunol Immunother 2013;62:1575-1585. https://doi.org/10.1007/s00262-013-1460-4
  42. Lv L, Pan K, Li XD, She KL, Zhao JJ, Wang W, Chen JG, Chen YB, Yun JP, Xia JC. The accumulation and prognosis value of tumor infiltrating IL-17 producing cells in esophageal squamous cell carcinoma. PLoS One 2011;6:e18219.
  43. Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, Xue X, Wei G, Liu X, Fang G. The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 2008;374:533-537. https://doi.org/10.1016/j.bbrc.2008.07.060
  44. Yamada Y, Saito H, Ikeguchi M. Prevalence and clinical relevance of Th17 cells in patients with gastric cancer. J Surg Res 2012;178:685-691. https://doi.org/10.1016/j.jss.2012.07.055
  45. Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, Wu C, Li SP, Zheng L. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 2009;50:980-989. https://doi.org/10.1016/j.jhep.2008.12.033
  46. Liao R, Sun J, Wu H, Yi Y, Wang JX, He HW, Cai XY, Zhou J, Cheng YF, Fan J, et al. High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. J Exp Clin Cancer Res 2013;32:3.
  47. Yan J, Liu XL, Xiao G, Li NL, Deng YN, Han LZ, Yin LC, Ling LJ, Liu LX. Prevalence and clinical relevance of T-helper cells, Th17 and Th1, in hepatitis B virus-related hepatocellular carcinoma. PLoS One 2014;9:e96080.
  48. Ye ZJ, Zhou Q, Gu YY, Qin SM, Ma WL, Xin JB, Tao XN, Shi HZ. Generation and differentiation of IL-17-producing CD4+ T cells in malignant pleural effusion. J Immunol 2010;185:6348-6354. https://doi.org/10.4049/jimmunol.1001728
  49. Gong Y, Chen SX, Gao BA, Yao RC, Guan L. Cell origins and significance of IL-17 in malignant pleural effusion. Clin Transl Oncol 2014;16:807-813. https://doi.org/10.1007/s12094-013-1152-8
  50. Bao Z, Lu G, Cui D, Yao Y, Yang G, Zhou J. IL-17A-producing T cells are associated with the progression of lung adenocarcinoma. Oncol Rep 2016;36:641-650. https://doi.org/10.3892/or.2016.4837
  51. Zelba H, Weide B, Martens A, Derhovanessian E, Bailur JK, Kyzirakos C, Pflugfelder A, Eigentler TK, Di Giacomo AM, Maio M, et al. Circulating CD4+ T cells that produce IL4 or IL17 when stimulated by Melan-A but not by NY-ESO-1 have negative impacts on survival of patients with stage IV melanoma. Clin Cancer Res 2014;20:4390-4399. https://doi.org/10.1158/1078-0432.CCR-14-1015
  52. Dhodapkar KM, Barbuto S, Matthews P, Kukreja A, Mazumder A, Vesole D, Jagannath S, Dhodapkar MV. Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma. Blood 2008;112:2878-2885.
  53. Shen CJ, Yuan ZH, Liu YX, Hu GY. Increased numbers of T helper 17 cells and the correlation with clinicopathological characteristics in multiple myeloma. J Int Med Res 2012;40:556-564. https://doi.org/10.1177/147323001204000217
  54. Zhang YL, Li J, Mo HY, Qiu F, Zheng LM, Qian CN, Zeng YX. Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways. Mol Cancer 2010;9:4.
  55. Li J, Mo HY, Xiong G, Zhang L, He J, Huang ZF, Liu ZW, Chen QY, Du ZM, Zheng LM, et al. Tumor microenvironment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem 2012;287:35484-35495. https://doi.org/10.1074/jbc.M112.367532
  56. Xu C, Yu L, Zhan P, Zhang Y. Elevated pleural effusion IL-17 is a diagnostic marker and outcome predictor in lung cancer patients. Eur J Med Res 2014;19:23.
  57. Chen X, Wan J, Liu J, Xie W, Diao X, Xu J, Zhu B, Chen Z. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer 2010;69:348-354. https://doi.org/10.1016/j.lungcan.2009.11.013
  58. Miyahara Y, Odunsi K, Chen W, Peng G, Matsuzaki J, Wang RF. Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci U S A 2008;105:15505-15510. https://doi.org/10.1073/pnas.0710686105
  59. Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 2009;114:1141-1149.
  60. He S, Fei M, Wu Y, Zheng D, Wan D, Wang L, Li D. Distribution and clinical significance of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients. Int J Mol Sci 2011;12:7424-7437. https://doi.org/10.3390/ijms12117424
  61. Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 2008;14:3254-3261. https://doi.org/10.1158/1078-0432.CCR-07-5164
  62. Derhovanessian E, Adams V, Hahnel K, Groeger A, Pandha H, Ward S, Pawelec G. Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients. Int J Cancer 2009;125:1372-1379. https://doi.org/10.1002/ijc.24497
  63. Huang Y, Wang J, Jia P, Li X, Pei G, Wang C, Fang X, Zhao Z, Cai Z, Yi X, et al. Clonal architectures predict clinical outcome in clear cell renal cell carcinoma. Nat Commun 2019;10:1245.
  64. Koyama K, Kagamu H, Miura S, Hiura T, Miyabayashi T, Itoh R, Kuriyama H, Tanaka H, Tanaka J, Yoshizawa H, et al. Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage. Clin Cancer Res 2008;14:6770-6779. https://doi.org/10.1158/1078-0432.CCR-08-1156
  65. Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G. Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 2010;184:1630-1641. https://doi.org/10.4049/jimmunol.0902813
  66. Chen D, Jiang R, Mao C, Shi L, Wang S, Yu L, Hu Q, Dai D, Xu H. Chemokine/chemokine receptor interactions contribute to the accumulation of Th17 cells in patients with esophageal squamous cell carcinoma. Hum Immunol 2012;73:1068-1072. https://doi.org/10.1016/j.humimm.2012.07.333
  67. Yu Q, Lou XM, He Y. Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway. PLoS One 2015;10:e0120855.
  68. Pan B, Shen J, Cao J, Zhou Y, Shang L, Jin S, Cao S, Che D, Liu F, Yu Y. Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer. Sci Rep 2015;5:16053.
  69. Li J, Huang ZF, Xiong G, Mo HY, Qiu F, Mai HQ, Chen QY, He J, Chen SP, Zheng LM, et al. Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma. J Transl Med 2011;9:189.
  70. Zhuang Y, Peng LS, Zhao YL, Shi Y, Mao XH, Chen W, Pang KC, Liu XF, Liu T, Zhang JY, et al. CD8+ T cells that produce interleukin-17 regulate myeloid-derived suppressor cells and are associated with survival time of patients with gastric cancer. Gastroenterology 2012;143:951-62.e8. https://doi.org/10.1053/j.gastro.2012.06.010
  71. Lee MH, Tung-Chieh Chang J, Liao CT, Chen YS, Kuo ML, Shen CR. Interleukin 17 and peripheral IL-17-expressing T cells are negatively correlated with the overall survival of head and neck cancer patients. Oncotarget 2018;9:9825-9837. https://doi.org/10.18632/oncotarget.23934
  72. Hinrichs CS, Kaiser A, Paulos CM, Cassard L, Sanchez-Perez L, Heemskerk B, Wrzesinski C, Borman ZA, Muranski P, Restifo NP. Type 17 CD8+ T cells display enhanced antitumor immunity. Blood 2009;114:596-599.
  73. Tajima M, Wakita D, Satoh T, Kitamura H, Nishimura T. IL-17/IFN-γ double producing CD8+ T (Tc17/IFN-γ) cells: a novel cytotoxic T-cell subset converted from Tc17 cells by IL-12. Int Immunol 2011;23:751-759. https://doi.org/10.1093/intimm/dxr086
  74. Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, et al. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity 2011;35:972-985. https://doi.org/10.1016/j.immuni.2011.09.019
  75. Yu Y, Cho HI, Wang D, Kaosaard K, Anasetti C, Celis E, Yu XZ. Adoptive transfer of Tc1 or Tc17 cells elicits antitumor immunity against established melanoma through distinct mechanisms. J Immunol 2013;190:1873-1881.
  76. Bowers JS, Nelson MH, Majchrzak K, Bailey SR, Rohrer B, Kaiser AD, Atkinson C, Gattinoni L, Paulos CM. Th17 cells are refractory to senescence and retain robust antitumor activity after long-term ex vivo expansion. JCI Insight 2017;2:e90772.
  77. Hu X, Majchrzak K, Liu X, Wyatt MM, Spooner CJ, Moisan J, Zou W, Carter LL, Paulos CM. In vitro priming of adoptively transferred T cells with a RORγ agonist confers durable memory and stemness in vivo. Cancer Res 2018;78:3888-3898.
  78. Wu P, Wu D, Ni C, Ye J, Chen W, Hu G, Wang Z, Wang C, Zhang Z, Xia W, et al. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 2014;40:785-800. https://doi.org/10.1016/j.immuni.2014.03.013
  79. Daley D, Zambirinis CP, Seifert L, Akkad N, Mohan N, Werba G, Barilla R, Torres-Hernandez A, Hundeyin M, Mani VR, et al. γδ T cells support pancreatic oncogenesis by restraining αβ T cell activation. Cell 2016;166:1485-1499.e15. https://doi.org/10.1016/j.cell.2016.07.046
  80. Kwon DI, Lee YJ. Lineage differentiation program of invariant natural killer T cells. Immune Netw 2017;17:365-377. https://doi.org/10.4110/in.2017.17.6.365
  81. Crosby CM, Kronenberg M. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol 2018;18:559-574. https://doi.org/10.1038/s41577-018-0034-2
  82. Kim CH. Control of innate and adaptive lymphocytes by the RAR-retinoic acid axis. Immune Netw 2018;18:e1.
  83. Bruchard M, Ghiringhelli F. Deciphering the roles of innate lymphoid cells in cancer. Front Immunol 2019;10:656.
  84. Koh J, Kim HY, Lee Y, Park IK, Kang CH, Kim YT, Kim JE, Choi M, Lee WW, Jeon YK, et al. IL23- producing human lung cancer cells promote tumor growth via conversion of innate lymphoid cell 1 (ILC1) into ILC3. Clin Cancer Res 2019;25:4026-4037. https://doi.org/10.1158/1078-0432.CCR-18-3458
  85. Zhu X, Mulcahy LA, Mohammed RA, Lee AH, Franks HA, Kilpatrick L, Yilmazer A, Paish EC, Ellis IO, Patel PM, et al. IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines. Breast Cancer Res 2008;10:R95.
  86. Vykhovanets EV, Maclennan GT, Vykhovanets OV, Gupta S. IL-17 Expression by macrophages is associated with proliferative inflammatory atrophy lesions in prostate cancer patients. Int J Clin Exp Pathol 2011;4:552-565.
  87. Chen X, Churchill MJ, Nagar KK, Tailor YH, Chu T, Rush BS, Jiang Z, Wang EB, Renz BW, Wang H, et al. IL-17 producing mast cells promote the expansion of myeloid-derived suppressor cells in a mouse allergy model of colorectal cancer. Oncotarget 2015;6:32966-32979. https://doi.org/10.18632/oncotarget.5435
  88. Tu JF, Pan HY, Ying XH, Lou J, Ji JS, Zou H. Mast cells comprise the major of interleukin 17-producing cells and predict a poor prognosis in hepatocellular carcinoma. Medicine (Baltimore) 2016;95:e3220.
  89. Liu X, Jin H, Zhang G, Lin X, Chen C, Sun J, Zhang Y, Zhang Q, Yu J. Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients. PLoS One 2014;9:e106834.
  90. Spolski R, Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 2008;26:57-79. https://doi.org/10.1146/annurev.immunol.26.021607.090316
  91. Petrella TM, Tozer R, Belanger K, Savage KJ, Wong R, Smylie M, Kamel-Reid S, Tron V, Chen BE, Hunder NN, et al. Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol 2012;30:3396-3401. https://doi.org/10.1200/JCO.2011.40.0655
  92. Petrella TM, Mihalcioiu CL, McWhirter E, Belanger K, Savage KJ, Song X, Hamid O, Cheng T, Davis ML, Lee CW, et al. Final efficacy results of NCIC CTG IND.202: a randomized phase II study of recombinant interleukin-21 (rIL21) in patients with recurrent or metastatic melanoma (MM). J Clin Oncol 2013;31:9032.
  93. Chapuis AG, Lee SM, Thompson JA, Roberts IM, Margolin KA, Bhatia S, Sloan HL, Lai I, Wagener F, Shibuya K, et al. Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. J Exp Med 2016;213:1133-1139. https://doi.org/10.1084/jem.20152021
  94. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 2009;10:857-863. https://doi.org/10.1038/ni.1767
  95. Jin M, Yoon J. From bench to clinic: the potential of therapeutic targeting of the IL-22 signaling pathway in atopic dermatitis. Immune Netw 2018;18:e42.
  96. Nardinocchi L, Sonego G, Passarelli F, Avitabile S, Scarponi C, Failla CM, Simoni S, Albanesi C, Cavani A. Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer. Eur J Immunol 2015;45:922-931. https://doi.org/10.1002/eji.201445052
  97. Eyerich K, Dimartino V, Cavani A. IL-17 and IL-22 in immunity: driving protection and pathology. Eur J Immunol 2017;47:607-614. https://doi.org/10.1002/eji.201646723
  98. Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, Gao Y, Yao A, Wang X, Yu L, et al. IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer 2013;13:59.
  99. Lim C, Savan R. The role of the IL-22/IL-22R1 axis in cancer. Cytokine Growth Factor Rev 2014;25:257-271. https://doi.org/10.1016/j.cytogfr.2014.04.005
  100. Wen Z, Liao Q, Zhao J, Hu Y, You L, Lu Z, Jia C, Wei Y, Zhao Y. High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma. Ann Surg Oncol 2014;21:125-132. https://doi.org/10.1245/s10434-013-3322-x
  101. Zhang W, Chen Y, Wei H, Zheng C, Sun R, Zhang J, Tian Z. Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. Clin Cancer Res 2008;14:6432-6439. https://doi.org/10.1158/1078-0432.CCR-07-4401
  102. Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 2012;21:836-847. https://doi.org/10.1016/j.ccr.2012.04.024
  103. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 2012;21:822-835. https://doi.org/10.1016/j.ccr.2012.04.025
  104. Su S, Liu Q, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014;25:605-620. https://doi.org/10.1016/j.ccr.2014.03.021
  105. Chen Y, Zhao Z, Chen Y, Lv Z, Ding X, Wang R, Xiao H, Hou C, Shen B, Feng J, et al. An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer. Sci Rep 2017;7:8265.
  106. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009;31:787-798. https://doi.org/10.1016/j.immuni.2009.09.014
  107. Ankathatti Munegowda M, Deng Y, Mulligan SJ, Xiang J. Th17 and Th17-stimulated CD8+ T cells play a distinct role in Th17-induced preventive and therapeutic antitumor immunity. Cancer Immunol Immunother 2011;60:1473-1484. https://doi.org/10.1007/s00262-011-1054-y
  108. Qian X, Gu L, Ning H, Zhang Y, Hsueh EC, Fu M, Hu X, Wei L, Hoft DF, Liu J. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 via tumor-secreted prostaglandin E2. J Immunol 2013;190:5894-5902. https://doi.org/10.4049/jimmunol.1203141
  109. Numasaki M, Watanabe M, Suzuki T, Takahashi H, Nakamura A, McAllister F, Hishinuma T, Goto J, Lotze MT, Kolls JK, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol 2005;175:6177-6189. https://doi.org/10.4049/jimmunol.175.9.6177
  110. Lee JW, Wang P, Kattah MG, Youssef S, Steinman L, DeFea K, Straus DS. Differential regulation of chemokines by IL-17 in colonic epithelial cells. J Immunol 2008;181:6536-6545. https://doi.org/10.4049/jimmunol.181.9.6536
  111. Kim CH, Park J, Kim M. Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw 2014;14:277-288. https://doi.org/10.4110/in.2014.14.6.277
  112. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009;15:1016-1022. https://doi.org/10.1038/nm.2015
  113. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012;491:254-258. https://doi.org/10.1038/nature11465
  114. Chan IH, Jain R, Tessmer MS, Gorman D, Mangadu R, Sathe M, Vives F, Moon C, Penaflor E, Turner S, et al. Interleukin-23 is sufficient to induce rapid de novo gut tumorigenesis, independent of carcinogens, through activation of innate lymphoid cells. Mucosal Immunol 2014;7:842-856. https://doi.org/10.1038/mi.2013.101
  115. Bagheri N, Azadegan-Dehkordi F, Shirzad H, Rafieian-Kopaei M, Rahimian G, Razavi A. The biological functions of IL-17 in different clinical expressions of Helicobacter pylori-infection. Microb Pathog 2015;81:33-38. https://doi.org/10.1016/j.micpath.2015.03.010
  116. McAllister F, Bailey JM, Alsina J, Nirschl CJ, Sharma R, Fan H, Rattigan Y, Roeser JC, Lankapalli RH, Zhang H, et al. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer Cell 2014;25:621-637. https://doi.org/10.1016/j.ccr.2014.03.014
  117. Li Q, Anderson CD, Egilmez NK. Inhaled IL-10 suppresses lung tumorigenesis via abrogation of inflammatory macrophage-Th17 cell axis. J Immunol 2018;201:2842-2850. https://doi.org/10.4049/jimmunol.1800141
  118. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL6-Stat3 signaling pathway. J Exp Med 2009;206:1457-1464. https://doi.org/10.1084/jem.20090207
  119. Chen X, Cai G, Liu C, Zhao J, Gu C, Wu L, Hamilton TA, Zhang CJ, Ko J, Zhu L, et al. IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells. J Exp Med 2019;216:195-214. https://doi.org/10.1084/jem.20171849
  120. Fanok MH, Sun A, Fogli LK, Narendran V, Eckstein M, Kannan K, Dolgalev I, Lazaris C, Heguy A, Laird ME, et al. Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of cutaneous T-cell lymphoma. J Invest Dermatol 2018;138:1116-1125. https://doi.org/10.1016/j.jid.2017.10.028
  121. Haudenschild D, Moseley T, Rose L, Reddi AH. Soluble and transmembrane isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer. J Biol Chem 2002;277:4309-4316. https://doi.org/10.1074/jbc.M109372200
  122. Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, Marberger MJ. Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate 2003;56:171-182. https://doi.org/10.1002/pros.10238
  123. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007;7:41-51. https://doi.org/10.1038/nri1995
  124. Li J, Lau GK, Chen L, Dong SS, Lan HY, Huang XR, Li Y, Luk JM, Yuan YF, Guan XY. Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression. PLoS One 2011;6:e21816.
  125. Yang B, Kang H, Fung A, Zhao H, Wang T, Ma D. The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis. Mediators Inflamm 2014;2014:623759.
  126. Xiang T, Long H, He L, Han X, Lin K, Liang Z, Zhuo W, Xie R, Zhu B. Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer. Oncogene 2015;34:165-176. https://doi.org/10.1038/onc.2013.537
  127. Zhang Q, Liu S, Parajuli KR, Zhang W, Zhang K, Mo Z, Liu J, Chen Z, Yang S, Wang AR, et al. Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene 2017;36:687-699. https://doi.org/10.1038/onc.2016.240
  128. Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, Levy DE, Settleman J, Engelman JA, Bardeesy N. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011;71:5020-5029.
  129. Ho PL, Lay EJ, Jian W, Parra D, Chan KS. Stat3 activation in urothelial stem cells leads to direct progression to invasive bladder cancer. Cancer Res 2012;72:3135-3142.
  130. Punt S, Langenhoff JM, Putter H, Fleuren GJ, Gorter A, Jordanova ES. The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review. OncoImmunology 2015;4:e984547.
  131. Park YJ, Kuen DS, Chung Y. Future prospects of immune checkpoint blockade in cancer: from response prediction to overcoming resistance. Exp Mol Med 2018;50:109.
  132. Cochaud S, Giustiniani J, Thomas C, Laprevotte E, Garbar C, Savoye AM, Cure H, Mascaux C, Alberici G, Bonnefoy N, et al. IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2. Sci Rep 2013;3:3456.
  133. Sui G, Qiu Y, Yu H, Kong Q, Zhen B. Interleukin-17 promotes the development of cisplatin resistance in colorectal cancer. Oncol Lett 2019;17:944-950.
  134. Chung AS, Wu X, Zhuang G, Ngu H, Kasman I, Zhang J, Vernes JM, Jiang Z, Meng YG, Peale FV, et al. An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nat Med 2013;19:1114-1123. https://doi.org/10.1038/nm.3291
  135. Nunez S, Saez JJ, Fernandez D, Flores-Santibanez F, Alvarez K, Tejon G, Ruiz P, Maldonado P, Hidalgo Y, Manriquez V, et al. T helper type 17 cells contribute to anti-tumour immunity and promote the recruitment of T helper type 1 cells to the tumour. Immunology 2013;139:61-71. https://doi.org/10.1111/imm.12055
  136. Majchrzak K, Nelson MH, Bailey SR, Bowers JS, Yu XZ, Rubinstein MP, Himes RA, Paulos CM. Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic. Cancer Immunol Immunother 2016;65:247-259. https://doi.org/10.1007/s00262-016-1797-6
  137. Liu J, Zhou G, Zhang L, Zhao Q. Building Potent Chimeric Antigen Receptor T Cells With CRISPR Genome Editing. Front Immunol 2019;10:456.
  138. Cheng J, Zhao L, Zhang Y, Qin Y, Guan Y, Zhang T, Liu C, Zhou J. Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies. Front Oncol 2019;9:1237.
  139. Chung Y, Qin H, Kang CY, Kim S, Kwak LW, Dong C. An NKT-mediated autologous vaccine generates CD4 T-cell dependent potent antilymphoma immunity. Blood 2007;110:2013-2019.
  140. Min B, Choi H, Her JH, Jung MY, Kim HJ, Jung MY, Lee EK, Cho SY, Hwang YK, Shin EC. Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy. Immune Netw 2018;18:e31.
  141. Mahalingam D, Wang JS, Hamilton EP, Sarantopoulos J, Nemunaitis J, Weems G, Carter L, Hu X, Schreeder M, Wilkins HJ. Phase 1 open-label, multicenter study of first-in-class RORγ agonist LYC-55716 (cintirorgon): safety, tolerability, and preliminary evidence of antitumor activity. Clin Cancer Res 2019;25:3508-3516. https://doi.org/10.1158/1078-0432.CCR-18-3185
  142. Bie Q, Sun C, Gong A, Li C, Su Z, Zheng D, Ji X, Wu Y, Guo Q, Wang S, et al. Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer. Sci Rep 2016;6:25447.
  143. Majchrzak K, Nelson MH, Bowers JS, Bailey SR, Wyatt MM, Wrangle JM, Rubinstein MP, Varela JC, Li Z, Himes RA, et al. β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity. JCI Insight 2017;2:90547.
  144. Guedan S, Chen X, Madar A, Carpenito C, McGettigan SE, Frigault MJ, Lee J, Posey AD Jr, Scholler J, Scholler N, et al. ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells. Blood 2014;124:1070-1080.
  145. Lee M, Rhee I. Cytokine Signaling in Tumor Progression. Immune Netw 2017;17:214-227. https://doi.org/10.4110/in.2017.17.4.214