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Immunologic Research

Erschienen in:

24.07.2021 | Review

Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy

verfasst von: Yin Qianmei, Su Zehong, Wang Guang, Li Hui, Gaojian Lian

Erschienen in: Immunologic Research | Ausgabe 5/2021

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Abstract

Th17 and Treg cells play an important role in regulating tissue inflammation and maintaining the stability of the immune system. They regulate inflammatory responses, participate in the occurrence and development of autoimmune diseases and tumors, and determine the disease progress. Malignant tumor is one of the diseases with the highest mortality rate in the world. However, the efficacy of traditional treatment is limited, so it is necessary to find safe and efficient treatment methods. Studies have shown that the balance of Th17/Treg cells plays a critical role in tumor progression. In this paper, we review the antitumor and tumor-suppressing effects of Th17/Treg cells, and new strategies for tumor therapy, combined with new research hotspots such as immune checkpoint therapy, miRNA-related gene therapy, and metabolic pathway regulation of Th17/Treg cell differentiation and tumor generation. The synergistic therapy is expected to be widely used in the future clinical practice, providing a new choice for the prevention and treatment of malignant tumors.

Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278(3):1910–4. https://doi.org/10.1074/jbc.M207577200.CrossRefPubMed

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32. https://doi.org/10.1038/ni1254.CrossRefPubMed

Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6(11):1133–41. https://doi.org/10.1038/ni1261.CrossRefPubMedPubMedCentral

Qin H, Wang L, Feng T, Elson CO, Niyongere SA, Lee SJ, et al. TGF-beta promotes Th17 cell development through inhibition of SOCS3. J Immunol. 2009;183(1):97–105. https://doi.org/10.4049/jimmunol.0801986.CrossRefPubMed

Mailer RK, Joly AL, Liu S, Elias S, Tegner J, Andersson J. IL-1β promotes Th17 differentiation by inducing alternative splicing of FOXP3. Sci Rep. 2015;5:14674. https://doi.org/10.1038/srep14674.CrossRefPubMedPubMedCentral

Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol. 2007;8(9):942–9. https://doi.org/10.1038/ni1496.CrossRefPubMed

Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8(9):950–7. https://doi.org/10.1038/ni1497.CrossRefPubMed

Ghiringhelli F, Bruchard M, Chalmin F, Rébé C. Production of adenosine by ectonucleotidases: a key factor in tumor immunoescape. J Biomed Biotechnol. 2012;2012:473712. https://doi.org/10.1155/2012/473712.CrossRefPubMedPubMedCentral

Chalmin F, Mignot G, Bruchard M, Chevriaux A, Végran F, Hichami A, et al. Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression. Immunity. 2012;36(3):362–73. https://doi.org/10.1016/j.immuni.2011.12.019.CrossRefPubMed

10.

Obermajer N, Wong JL, Edwards RP, Chen K, Scott M, Khader S, et al. Induction and stability of human Th17 cells require endogenous NOS2 and cGMP-dependent NO signaling. J Exp Med. 2013;210(7):1433–45. https://doi.org/10.1084/jem.20121277.CrossRefPubMedPubMedCentral

11.

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330–6. https://doi.org/10.1038/ni904.CrossRefPubMed

12.

Cai J, Wang D, Zhang G, Guo X. The role Of PD-1/PD-L1 axis in treg development and function: implications for cancer immunotherapy. Onco Targets Ther. 2019;12:8437–45. https://doi.org/10.2147/ott.S221340.CrossRefPubMedPubMedCentral

13.

Ballke C, Gran E, Baekkevold ES, Jahnsen FL. Characterization of regulatory T-Cell markers in CD4+ T Cells of the upper airway mucosa. PLoS ONE. 2016;11(2):e0148826. https://doi.org/10.1371/journal.pone.0148826.CrossRefPubMedPubMedCentral

14.

Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87–113. https://doi.org/10.1111/j.1600-065X.2008.00628.x.CrossRefPubMedPubMedCentral

15.

Wang Y, Xing F, Ye S, Xiao J, Di J, Zeng S, et al. Jagged-1 signaling suppresses the IL-6 and TGF-β treatment-induced Th17 cell differentiation via the reduction of RORγt/IL-17A/IL-17F/IL-23a/IL-12rb1. Sci Rep. 2015;5:8234. https://doi.org/10.1038/srep08234.CrossRefPubMedPubMedCentral

16.

Li MO, Rudensky AY. T cell receptor signalling in the control of regulatory T cell differentiation and function. Nat Rev Immunol. 2016;16(4):220–33. https://doi.org/10.1038/nri.2016.26.CrossRefPubMedPubMedCentral

17.

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32. https://doi.org/10.3322/caac.21338.CrossRefPubMed

18.

Guéry L, Hugues S. Th17 Cell Plasticity and Functions in Cancer Immunity. Biomed Res Int. 2015;2015:314620. https://doi.org/10.1155/2015/314620.CrossRefPubMedPubMedCentral

19.

Li X, Wang Y, Han C, Li P, Zhang H. Colorectal cancer progression is associated with accumulation of Th17 lymphocytes in tumor tissues and increased serum levels of interleukin-6. Tohoku J Exp Med. 2014;233(3):175–82. https://doi.org/10.1620/tjem.233.175.CrossRefPubMed

20.

He G, Zhang B, Zhang B, Qiao L, Tian Z, Zhai G, et al. Th17 cells and IL-17 are increased in patients with brain metastases from the primary lung cancer. Chin J Lung Cancer. 2013;16(9):476–81. https://doi.org/10.3779/j.issn.1009-3419.2013.09.07.CrossRef

21.

Salazar Y, Zheng X, Brunn D, Raifer H, Picard F, Zhang Y, et al. Microenvironmental Th9 and Th17 lymphocytes induce metastatic spreading in lung cancer. J Clin Investig. 2020;130(7):3560–75. https://doi.org/10.1172/jci124037.CrossRefPubMedPubMedCentral

22.

Ma K, Yang L, Shen R, Kong B, Chen W, Liang J, et al. Th17 cells regulate the production of CXCL1 in breast cancer. Int Immunopharmacol. 2018;56:320–9. https://doi.org/10.1016/j.intimp.2018.01.026.CrossRefPubMed

23.

Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A, et al. TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer. Nat Commun. 2020;11(1):2608. https://doi.org/10.1038/s41467-020-16363-w.CrossRefPubMedPubMedCentral

24.

Li B, Wang X, Choi IY, Wang YC, Liu S, Pham AT, et al. miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity. J Clin Investig. 2017;127(10):3702–16. https://doi.org/10.1172/jci94012.CrossRefPubMedPubMedCentral

25.

Zhang Y, Wang ZC, Zhang ZS, Chen F. MicroRNA-155 regulates cervical cancer via inducing Th17/Treg imbalance. Eur Rev Med Pharmacol Sci. 2018;22(12):3719–26. https://doi.org/10.26355/eurrev_201806_15251.CrossRefPubMed

26.

Rossi M, Altomare E, Botta C, Gallo Cantafio ME, Sarvide S, Caracciolo D, et al. miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma. Leukemia. 2021;35(3):823–34. https://doi.org/10.1038/s41375-020-0947-1.CrossRefPubMed

27.

Zheng X, Dong L, Wang K, Zou H, Zhao S, Wang Y, et al. MiR-21 Participates in the PD-1/PD-L1 pathway-mediated imbalance of Th17/Treg Cells in patients after gastric cancer resection. Ann Surg Oncol. 2019;26(3):884–93. https://doi.org/10.1245/s10434-018-07117-6.CrossRefPubMed

28.

Wang T, Liu L, Chen X, Shen Y, Lian G, Shah N, et al. MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to an ROS augmenting agent. Cell Death Dis. 2018;9(2):220. https://doi.org/10.1038/s41419-018-0295-5.CrossRefPubMedPubMedCentral

29.

Sciacovelli M, Gaude E, Hilvo M, Frezza C. The metabolic alterations of cancer cells. Methods Enzymol. 2014;542:1–23. https://doi.org/10.1016/b978-0-12-416618-9.00001-7.CrossRefPubMed

30.

Weinberg SE, Chandel NS. Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol. 2015;11(1):9–15. https://doi.org/10.1038/nchembio.1712.CrossRefPubMedPubMedCentral

31.

Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G. Metabolic targets for cancer therapy. Nat Rev Drug Discovery. 2013;12(11):829–46. https://doi.org/10.1038/nrd4145.CrossRefPubMed

32.

McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends Immunol. 2006;27(1):17–23. https://doi.org/10.1016/j.it.2005.10.003.CrossRefPubMed

33.

Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Can Res. 2011;71(4):1263–71. https://doi.org/10.1158/0008-5472.Can-10-2907.CrossRef

34.

Chang SH. T helper 17 (Th17) cells and interleukin-17 (IL-17) in cancer. Arch Pharmacal Res. 2019;42(7):549–59. https://doi.org/10.1007/s12272-019-01146-9.CrossRef

35.

Chen X, Wan J, Liu J, Xie W, Diao X, Xu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer. 2010;69(3):348–54. https://doi.org/10.1016/j.lungcan.2009.11.013.CrossRefPubMed

36.

Yamada Y, Saito H, Ikeguchi M. Prevalence and clinical relevance of Th17 cells in patients with gastric cancer. J Surg Res. 2012;178(2):685–91. https://doi.org/10.1016/j.jss.2012.07.055.CrossRefPubMed

37.

Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol. 2009;50(5):980–9. https://doi.org/10.1016/j.jhep.2008.12.033.CrossRefPubMed

38.

Maruyama T, Kono K, Mizukami Y, Kawaguchi Y, Mimura K, Watanabe M, et al. Distribution of Th17 cells and FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes and peripheral blood lymphocytes in patients with gastric cancer. Cancer Sci. 2010;101(9):1947–54. https://doi.org/10.1111/j.1349-7006.2010.01624.x.CrossRefPubMed

39.

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 USA. 2008;105(40):15505–10. https://doi.org/10.1073/pnas.0710686105.CrossRefPubMedPubMedCentral

40.

Sharp SP, Avram D, Stain SC, Lee EC. Local and systemic Th17 immune response associated with advanced stage colon cancer. J Surg Res. 2017;208:180–6. https://doi.org/10.1016/j.jss.2016.09.038.CrossRefPubMed

41.

Wang K, Kim MK, Di Caro G, Wong J, Shalapour S, Wan J, et al. Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity. 2014;41(6):1052–63. https://doi.org/10.1016/j.immuni.2014.11.009.CrossRefPubMedPubMedCentral

42.

Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(6):1141–9. https://doi.org/10.1182/blood-2009-03-208249.CrossRefPubMedPubMedCentral

43.

DiPaolo RJ, Glass DD, Bijwaard KE, Shevach EM. CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells. J Immunol. 2005;175(11):7135–42. https://doi.org/10.4049/jimmunol.175.11.7135.CrossRefPubMed

44.

Kryczek I, Liu R, Wang G, Wu K, Shu X, Szeliga W, et al. FOXP3 defines regulatory T cells in human tumor and autoimmune disease. Can Res. 2009;69(9):3995–4000. https://doi.org/10.1158/0008-5472.Can-08-3804.CrossRef

45.

Guo J, Zhou X. Regulatory T cells turn pathogenic. Cell Mol Immunol. 2015;12(5):525–32. https://doi.org/10.1038/cmi.2015.12.CrossRefPubMedPubMedCentral

46.

Ou X, Zhang GT, Tian PK, Chen JS, Lin ZW, Xie Y, et al. Forkhead box P3 gene silencing inhibits the expression of chemokines and chemokine receptors associated with cell growth, migration, and apoptosis in hepatocellular carcinoma cells. Exp Ther Med. 2019;18(2):1091–8. https://doi.org/10.3892/etm.2019.7658.CrossRefPubMedPubMedCentral

47.

Shou J, Zhang Z, Lai Y, Chen Z, Huang J. Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs : a systematic review and meta-analysis. BMC Cancer. 2016;16(1):687. https://doi.org/10.1186/s12885-016-2732-0.CrossRefPubMedPubMedCentral

48.

Budhu S, Schaer DA, Li Y, Toledo-Crow R, Panageas K, Yang X, et al. Blockade of surface-bound TGF-β on regulatory T cells abrogates suppression of effector T cell function in the tumor microenvironment. Sci Signal. 2017;10(494):eaak9702. https://doi.org/10.1126/scisignal.aak9702.CrossRefPubMedPubMedCentral

49.

Knochelmann HM, Dwyer CJ, Bailey SR, Amaya SM, Elston DM, Mazza-McCrann JM, et al. When worlds collide: Th17 and Treg cells in cancer and autoimmunity. Cell Mol Immunol. 2018;15(5):458–69. https://doi.org/10.1038/s41423-018-0004-4.CrossRefPubMedPubMedCentral

50.

Khalife E, Khodadadi A, Talaeizadeh A, Rahimian L, Nemati M, Jafarzadeh A. Overexpression of Regulatory T Cell-Related Markers (FOXP3, CTLA-4 and GITR) by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer. Asian Pac J Cancer Prev. 2018;19(11):3019–25. https://doi.org/10.31557/apjcp.2018.19.11.3019.CrossRefPubMedPubMedCentral

51.

Maturu P, Jones D, Ruteshouser EC, Hu Q, Reynolds JM, Hicks J, et al. Role of Cyclooxygenase-2 pathway in creating an immunosuppressive microenvironment and in initiation and progression of Wilms’ Tumor. Neoplasia. 2017;19(3):237–49. https://doi.org/10.1016/j.neo.2016.07.009.CrossRefPubMedPubMedCentral

52.

Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-Dependent manner. Cell Rep. 2015;13(2):412–24. https://doi.org/10.1016/j.celrep.2015.08.077.CrossRefPubMedPubMedCentral

53.

Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9. https://doi.org/10.1038/nm1093.CrossRefPubMed

54.

Gai XD, Li C, Song Y, Lei YM, Yang BX. In situ analysis of FOXP3(+) regulatory T cells and myeloid dendritic cells in human colorectal cancer tissue and tumor-draining lymph node. Biomedical Rep. 2013;1(2):207–12. https://doi.org/10.3892/br.2012.35.CrossRef

55.

Loddenkemper C, Schernus M, Noutsias M, Stein H, Thiel E, Nagorsen D. In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. J Transl Med. 2006;4:52. https://doi.org/10.1186/1479-5876-4-52.CrossRefPubMedPubMedCentral

56.

Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol. 2009;27(2):186–92.

57.

Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18(12):1332–41. https://doi.org/10.1038/ni.3868.CrossRefPubMedPubMedCentral

58.

Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010;63(6):601–10. https://doi.org/10.1111/j.1600-0897.2010.00852.x.CrossRefPubMed

59.

Deng Y, Wang Z, Chang C, Lu L, Lau CS, Lu Q. Th9 cells and IL-9 in autoimmune disorders: pathogenesis and therapeutic potentials. Hum Immunol. 2017;78(2):120–8. https://doi.org/10.1016/j.humimm.2016.12.010.CrossRefPubMed

60.

Phillips JD, Knab LM, Blatner NR, Haghi L, DeCamp MM, Meyerson SL, et al. Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer. Cancer Immunol Immunother. 2015;64(9):1185–91. https://doi.org/10.1007/s00262-015-1725-1.CrossRefPubMedPubMedCentral

61.

Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, et al. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA. 2009;106(12):4793–8. https://doi.org/10.1073/pnas.0900408106.CrossRefPubMedPubMedCentral

62.

Kryczek I, Wu K, Zhao E, Wei S, Vatan L, Szeliga W, et al. IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer. J Immunol. 2011;186(7):4388–95. https://doi.org/10.4049/jimmunol.1003251.CrossRefPubMed

63.

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(3):1630–41. https://doi.org/10.4049/jimmunol.0902813.CrossRefPubMed

64.

Ye J, Su X, Hsueh EC, Zhang Y, Koenig JM, Hoft DF, et al. Human tumor-infiltrating Th17 cells have the capacity to differentiate into IFN-γ+ and FOXP3+ T cells with potent suppressive function. Eur J Immunol. 2011;41(4):936–51. https://doi.org/10.1002/eji.201040682.CrossRefPubMed

65.

Martin F, Apetoh L, Ghiringhelli F. Controversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity? Trends Mol Med. 2012;18(12):742–9. https://doi.org/10.1016/j.molmed.2012.09.007.CrossRefPubMed

66.

Fu LQ, Yang X, Cai MH, Yao JY, Jin WW, Mou YP, et al. Role of Treg/Th17 imbalance, microbiota and miRNAs in pancreatic cancer: therapeutic options. Crit Rev Immunol. 2020;40(1):75–92. https://doi.org/10.1615/CritRevImmunol.2020033631.CrossRefPubMed

67.

Zambirinis CP, Pushalkar S, Saxena D, Miller G. Pancreatic cancer, inflammation, and microbiome. Cancer J. 2014;20(3):195–202. https://doi.org/10.1097/ppo.0000000000000045.CrossRefPubMedPubMedCentral

68.

Bi L, Wu J, Ye A, Wu J, Yu K, Zhang S, et al. Increased Th17 cells and IL-17A exist in patients with B cell acute lymphoblastic leukemia and promote proliferation and resistance to daunorubicin through activation of Akt signaling. J Transl Med. 2016;14(1):132. https://doi.org/10.1186/s12967-016-0894-9.CrossRefPubMedPubMedCentral

69.

Marshall EA, Ng KW, Kung SH, Conway EM, Martinez VD, Halvorsen EC, et al. Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis. Mol Cancer. 2016;15(1):67. https://doi.org/10.1186/s12943-016-0551-1.CrossRefPubMedPubMedCentral

70.

Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620–7. https://doi.org/10.1182/blood-2002-05-1461.CrossRefPubMed

71.

Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med. 2009;206(7):1457–64. https://doi.org/10.1084/jem.20090207.CrossRefPubMedPubMedCentral

72.

Pan B, Shen J, Cao J, Zhou Y, Shang L, Jin S, et al. 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. https://doi.org/10.1038/srep16053.CrossRefPubMedPubMedCentral

73.

Amicarella F, Muraro MG, Hirt C, Cremonesi E, Padovan E, Mele V, et al. Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer. Gut. 2017;66(4):692–704. https://doi.org/10.1136/gutjnl-2015-310016.CrossRefPubMed

74.

Wu P, Wu D, Ni C, Ye J, Chen W, Hu G, et al. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity. 2014;40(5):785–800. https://doi.org/10.1016/j.immuni.2014.03.013.CrossRefPubMedPubMedCentral

75.

Phan-Lai V, Dang Y, Gad E, Childs J, Disis ML. The Antitumor Efficacy of IL2/IL21-Cultured Polyfunctional Neu-Specific T Cells Is TNFα/IL17 Dependent. Clin Cancer Res. 2016;22(9):2207–16. https://doi.org/10.1158/1078-0432.Ccr-15-2273.CrossRefPubMed

76.

Lim C, Savan R. The role of the IL-22/IL-22R1 axis in cancer. Cytokine Growth Factor Rev. 2014;25(3):257–71. https://doi.org/10.1016/j.cytogfr.2014.04.005.CrossRefPubMed

77.

Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood. 2008;112(2):362–73. https://doi.org/10.1182/blood-2007-11-120998.CrossRefPubMedPubMedCentral

78.

He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, et al. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. Blood. 2010;184(5):2281–8. https://doi.org/10.4049/jimmunol.0902574.CrossRef

79.

Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, et al. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity. 2011;35(6):972–85. https://doi.org/10.1016/j.immuni.2011.09.019.CrossRefPubMedPubMedCentral

80.

Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 2009;31(5):787–98. https://doi.org/10.1016/j.immuni.2009.09.014.CrossRefPubMedPubMedCentral

81.

Kryczek I, Wei S, Szeliga W, Vatan L, Zou W. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood. 2009;114(2):357–9. https://doi.org/10.1182/blood-2008-09-177360.CrossRefPubMedPubMedCentral

82.

Xu X, Wang R, Su Q, Huang H, Zhou P, Luan J, et al. Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma. Oncol Lett. 2016;12(3):1941–8. https://doi.org/10.3892/ol.2016.4854.CrossRefPubMedPubMedCentral

83.

Koyama K, Kagamu H, Miura S, Hiura T, Miyabayashi T, Itoh R, 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(21):6770–9. https://doi.org/10.1158/1078-0432.Ccr-08-1156.CrossRefPubMed

84.

Finotello F, Trajanoski Z. New strategies for cancer immunotherapy: targeting regulatory T cells. Genome Med. 2017;9(1):10. https://doi.org/10.1186/s13073-017-0402-8.CrossRefPubMedPubMedCentral

85.

Wu H, Li P, Shao N, Ma J, Ji M, Sun X, et al. Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia. Oncol Lett. 2012;3(5):1119–23. https://doi.org/10.3892/ol.2012.614.CrossRefPubMedPubMedCentral

86.

Betts G, Twohig J, Van den Broek M, Sierro S, Godkin A, Gallimore A. The impact of regulatory T cells on carcinogen-induced sarcogenesis. Br J Cancer. 2007;96(12):1849–54. https://doi.org/10.1038/sj.bjc.6603824.CrossRefPubMedPubMedCentral

87.

Hou F, Ma D, Cui B. Treg cells in different forms of uterine cancer. Clin Chim Acta. 2013;415:337–40. https://doi.org/10.1016/j.cca.2012.11.004.CrossRefPubMed

88.

Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 2011;475(7355):226–30. https://doi.org/10.1038/nature10169.CrossRefPubMed

89.

Yokobori T, Nishiyama M. TGF-β Signaling in Gastrointestinal Cancers: Progress in Basic and Clinical Research. J Clin Med. 2017;6(1):11. https://doi.org/10.3390/jcm6010011.CrossRefPubMedCentral

90.

Nicholl MB, Ledgewood CL, Chen X, Bai Q, Qin C, Cook KM, et al. IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor. Cytokine. 2014;70(2):126–33. https://doi.org/10.1016/j.cyto.2014.06.020.CrossRefPubMed

91.

Ni C, Fang QQ, Chen WZ, Jiang JX, Jiang Z, Ye J, et al. Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells. Signal Transduct Target Ther. 2020;5(1):41. https://doi.org/10.1038/s41392-020-0129-7.CrossRefPubMedPubMedCentral

92.

Ma SR, Deng WW, Liu JF, Mao L, Yu GT, Bu LL, et al. Blockade of adenosine A2A receptor enhances CD8(+) T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma. Mol Cancer. 2017;16(1):99. https://doi.org/10.1186/s12943-017-0665-0.CrossRefPubMedPubMedCentral

93.

Bos PD, Rudensky AY. Treg cells in cancer: a case of multiple personality disorder. Sci Transl Med. 2012;4(164):164fs44. https://doi.org/10.1126/scitranslmed.3005283.CrossRefPubMed

94.

Kumar P, Bhattacharya P, Prabhakar BS. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity. J Autoimmun. 2018;95:77–99. https://doi.org/10.1016/j.jaut.2018.08.007.CrossRefPubMedPubMedCentral

95.

Zappasodi R, Li Y, Abu-Akeel M, Qi J, Merghoub T. Abstract CT018: Intratumor and peripheral Treg modulation as a pharmacodynamic biomarker of the GITR agonist antibody TRX-518 in the first in-human trial. Cancer Res. 2017;77(Suppl 13):CT018–CT018.

96.

Zhang Y, Lazarus J, Steele NG, Yan W, Lee HJ, Nwosu ZC, et al. Regulatory T-cell depletion alters the tumor microenvironment and accelerates pancreatic carcinogenesis. Cancer Discov. 2020;10(3):422–39. https://doi.org/10.1158/2159-8290.Cd-19-0958.CrossRefPubMedPubMedCentral

97.

Zhou J, Li X, Wu X, Zhang T, Zhu Q, Wang X, et al. Exosomes released from tumor-associated macrophages transfer miRNAs That Induce a Treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res. 2018;6(12):1578–92. https://doi.org/10.1158/2326-6066.Cir-17-0479.CrossRefPubMed

98.

Kinoshita M, Kobayashi S, Gotoh K, Kubo M, Hayashi K, Iwagami Y, et al. Heterogeneity of Treg/Th17 according to cancer progression and modification in biliary tract cancers via self-producing cytokines. Dig Dis Sci. 2020;65(10):2937–48. https://doi.org/10.1007/s10620-019-06011-9.CrossRefPubMed

99.

Duan MC, Han W, Jin PW, Wei YP, Wei Q, Zhang LM, et al. Disturbed Th17/Treg balance in patients with non-small cell lung cancer. Inflammation. 2015;38(6):2156–65. https://doi.org/10.1007/s10753-015-0198-x.CrossRefPubMed

100.

Li L, Yang C, Zhao Z, Xu B, Zheng M, Zhang C, et al. Skewed T-helper (Th)1/2- and Th17/T regulatory-cell balances in patients with renal cell carcinoma. Mol Med Rep. 2015;11(2):947–53. https://doi.org/10.3892/mmr.2014.2778.CrossRefPubMed

101.

Zhang W, Hou F, Zhang Y, Tian Y, Jiao J, Ma D, et al. Changes of Th17/Tc17 and Th17/Treg cells in endometrial carcinoma. Gynecol Oncol. 2014;132(3):599–605. https://doi.org/10.1016/j.ygyno.2013.12.036.CrossRefPubMed

102.

Lin W, Niu Z, Zhang H, Kong Y, Wang Z, Yang X, et al. Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer. Int J Clin Exp Pathol. 2019;12(9):3604–12.PubMedPubMedCentral

103.

Lin W, Zhang HL, Niu ZY, Wang Z, Kong Y, Yang XS, et al. The disease stage-associated imbalance of Th1/Th2 and Th17/Treg in uterine cervical cancer patients and their recovery with the reduction of tumor burden. BMC Womens Health. 2020;20(1):126. https://doi.org/10.1186/s12905-020-00972-0.CrossRefPubMedPubMedCentral

104.

Chen Z, Ding J, Pang N, Du R, Meng W, Zhu Y, et al. The Th17/Treg balance and the expression of related cytokines in Uygur cervical cancer patients. Diagn Pathol. 2013;8:61. https://doi.org/10.1186/1746-1596-8-61.CrossRefPubMedPubMedCentral

105.

Wang X, Wang L, Mo Q, Dong Y, Wang G, Ji A. Changes of Th17/Treg cell and related cytokines in pancreatic cancer patients. Int J Clin Exp Pathol. 2015;8(5):5702–8.PubMedPubMedCentral

106.

Lan YT, Fan XP, Fan YC, Zhao J, Wang K. Change in the Treg/Th17 cell imbalance in hepatocellular carcinoma patients and its clinical value. Medicine. 2017;96(32):e7704. https://doi.org/10.1097/md.0000000000007704.CrossRefPubMedPubMedCentral

107.

Liu C, Tong Z, Tan J, Xin Z. Analysis of Treg/Th17 cells in patients with tongue squamous cell carcinoma. Exp Ther Med. 2019;18(3):2187–93. https://doi.org/10.3892/etm.2019.7814.CrossRefPubMedPubMedCentral

108.

Wang L, Zhang Y, Xie F. T-regulatory cell/T helper 17 cell imbalance functions as prognostic biomarker of oral squamous cell carcinoma - CONSORT. Medicine. 2020;99(49):e23145. https://doi.org/10.1097/md.0000000000023145.CrossRefPubMedPubMedCentral

109.

Li Q, Li Q, Chen J, Liu Y, Zhao X, Tan B, et al. Prevalence of Th17 and Treg cells in gastric cancer patients and its correlation with clinical parameters. Oncol Rep. 2013;30(3):1215–22. https://doi.org/10.3892/or.2013.2570.CrossRefPubMed

110.

Zhao L, Yang J, Wang HP, Liu RY. Imbalance in the Th17/Treg and cytokine environment in peripheral blood of patients with adenocarcinoma and squamous cell carcinoma. Medical Oncol. 2013;30(1):461. https://doi.org/10.1007/s12032-013-0461-7.CrossRef

111.

Meng X, Zhu S, Dong Q, Zhang S, Ma J, Zhou C. Expression of Th17/Treg related molecules in gastric cancer tissues. Turk J Gastroenterol. 2018;29(1):45–51. https://doi.org/10.5152/tjg.2018.17114.CrossRefPubMedPubMedCentral

112.

Huo W, Liu Y, Lei Y, Zhang Y, Huang Y, Mao Y, et al. Imbalanced spinal infiltration of Th17/Treg cells contributes to bone cancer pain via promoting microglial activation. Brain Behav Immun. 2019;79:139–51. https://doi.org/10.1016/j.bbi.2019.01.024.CrossRefPubMed

113.

Wu H, Zheng X, Dong L, Li C, Zhang M, Wang G, et al. Pir-B inhibits the DC function and disturbs the Th17/Treg balance in lung cancer murine model. Oncotarget. 2017;8(70):114710–21. https://doi.org/10.18632/oncotarget.21763.CrossRefPubMedPubMedCentral

114.

Downs-Canner S, Berkey S, Delgoffe GM, Edwards RP, Curiel T, Odunsi K, et al. Suppressive IL-17A(+)Foxp3(+) and ex-Th17 IL-17A(neg)Foxp3(+) T(reg) cells are a source of tumour-associated T(reg) cells. Nat Commun. 2017;8:14649. https://doi.org/10.1038/ncomms14649.CrossRefPubMedPubMedCentral

115.

Jiao S, Subudhi SK, Aparicio A, Ge Z, Guan B, Miura Y, et al. Differences in tumor microenvironment dictate t helper lineage polarization and response to immune checkpoint therapy. Cell. 2019;179(5):1177-90.e13. https://doi.org/10.1016/j.cell.2019.10.029.CrossRefPubMed

116.

Webb ES, Liu P, Baleeiro R, Lemoine NR, Yuan M, Wang YH. Immune checkpoint inhibitors in cancer therapy. J Biomed Res. 2018;32(5):317–26. https://doi.org/10.7555/jbr.31.20160168.CrossRefPubMed

117.

Mitsuiki N, Schwab C, Grimbacher B. What did we learn from CTLA-4 insufficiency on the human immune system? Immunol Rev. 2019;287(1):33–49. https://doi.org/10.1111/imr.12721.CrossRefPubMed

118.

Wang X, Guo G, Guan H, Yu Y, Lu J, Yu J. Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma. J Exp Clin Cancer Res. 2019;38(1):87. https://doi.org/10.1186/s13046-019-1085-3.CrossRefPubMedPubMedCentral

119.

Li Q, Ngo PT, Egilmez NK. Anti-PD-1 antibody-mediated activation of type 17 T-cells undermines checkpoint blockade therapy. Cancer Immunol. 2021;70(6):1789–96.

120.

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003;374(Pt 1):1–20. https://doi.org/10.1042/bj20030407.CrossRefPubMedPubMedCentral

121.

Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol. 2017;13(7):399–409. https://doi.org/10.1038/nrrheum.2017.83.CrossRefPubMed

122.

Morris JC, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Reiss M, et al. Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS ONE. 2014;9(3):e90353. https://doi.org/10.1371/journal.pone.0090353.CrossRefPubMedPubMedCentral

123.

Jaschinski F, Rothhammer T, Jachimczak P, Seitz C, Schneider A, Schlingensiepen KH. The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-β2. Curr Pharm Biotechnol. 2011;12(12):2203–13. https://doi.org/10.2174/138920111798808266.CrossRefPubMed

124.

Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R, et al. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis. PLoS ONE. 2013;8(4):e60914. https://doi.org/10.1371/journal.pone.0060914.CrossRefPubMedPubMedCentral

125.

Chatterjee M, Stühmer T, Herrmann P, Bommert K, Dörken B, Bargou RC. Combined disruption of both the MEK/ERK and the IL-6R/STAT3 pathways is required to induce apoptosis of multiple myeloma cells in the presence of bone marrow stromal cells. Blood. 2004;104(12):3712–21. https://doi.org/10.1182/blood-2004-04-1670.CrossRefPubMed

126.

Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, et al. Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res. 2009;15(17):5426–34. https://doi.org/10.1158/1078-0432.Ccr-09-0287.CrossRefPubMed

127.

Duffy J, Padovani F, Brunetti G, Noy P, Certa U, Hegner M. Towards personalised rapid label free miRNA detection for cancer and liver injury diagnostics in cell lysates and blood based samples. Nanoscale. 2018;10(26):12797–804. https://doi.org/10.1039/c8nr03604g.CrossRefPubMed

128.

Kutwin P, Konecki T, Borkowska EM, Traczyk-Borszyńska M, Jabłonowski Z. Urine miRNA as a potential biomarker for bladder cancer detection - a meta-analysis. Cent European J Urol. 2018;71(2):177–85. https://doi.org/10.5173/ceju.2018.1605.CrossRefPubMedPubMedCentral

129.

Jiang M, Li X, Quan X, Li X, Zhou B. Clinically correlated micrornas in the diagnosis of non-small cell lung cancer: a systematic review and meta-analysis. Biomed Res Int. 2018;2018:5930951. https://doi.org/10.1155/2018/5930951.CrossRefPubMedPubMedCentral

130.

Zhu B, Ju S, Chu H, Shen X, Zhang Y, Luo X, et al. The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma. Oncol Lett. 2018;15(5):6094–106. https://doi.org/10.3892/ol.2018.8157.CrossRefPubMedPubMedCentral

131.

Lu J, Zhan Y, Feng J, Luo J, Fan S. MicroRNAs associated with therapy of non-small cell lung cancer. Int J Biol Sci. 2018;14(4):390–7. https://doi.org/10.7150/ijbs.22243.CrossRefPubMedPubMedCentral

132.

Samiei H, Sadighi-Moghaddam B, Mohammadi S, Gharavi A, Abdolmaleki S, Khosravi A, et al. Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21. Immunol Res. 2019;67(2–3):212–22. https://doi.org/10.1007/s12026-019-09079-7.CrossRefPubMed

133.

Li T, Li M, Xu C, Xu X, Ding J, Cheng L, et al. miR-146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF-κB signaling by targeting TRAF6. Oncol Rep. 2019;41(5):2897–908. https://doi.org/10.3892/or.2019.7046.CrossRefPubMed

134.

Soheilifar MH, Vaseghi H, Seif F, Ariana M, Ghorbanifar S, Habibi N, et al. Concomitant overexpression of mir-182-5p and mir-182-3p raises the possibility of IL-17-producing Treg formation in breast cancer by targeting CD3d, ITK, FOXO1, and NFATs: A meta-analysis and experimental study. Cancer Sci. 2021;112(2):589–603. https://doi.org/10.1111/cas.14764.CrossRefPubMed

135.

Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, et al. TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012;22(3):291–303. https://doi.org/10.1016/j.ccr.2012.07.023.CrossRefPubMedPubMedCentral

136.

Migdalska-Sęk M, Góralska K, Jabłoński S, Kordiak J, Nawrot E, Kiszałkiewicz JM, et al. Evaluation of the relationship between the IL-17A gene expression level and regulatory miRNA-9 in relation to tumor progression in patients with non-small cell lung cancer: a pilot study. Mol Biol Rep. 2020;47(1):583–92.

137.

Chung YW, Bae HS, Song JY, Lee JK, Lee NW, Kim T, et al. Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients. Int J Gynecol Cancer. 2013;23(4):673–9. https://doi.org/10.1097/IGC.0b013e31828c166d.CrossRefPubMed

138.

Kishton RJ, Sukumar M, Restifo NP. Metabolic regulation of T cell longevity and function in tumor immunotherapy. Cell Metab. 2017;26(1):94–109. https://doi.org/10.1016/j.cmet.2017.06.016.CrossRefPubMedPubMedCentral

139.

Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, et al. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Investig. 2013;123(10):4479–88. https://doi.org/10.1172/jci69589.CrossRefPubMedPubMedCentral

140.

Xu R, Wu M, Liu S, Shang W, Li R, Xu J, et al. Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4(+) Treg cells in ovarian cancer cells microenvironment. Cell Death Dis. 2021;12(1):22. https://doi.org/10.1038/s41419-020-03272-5.CrossRefPubMedPubMedCentral

141.

Granchi C, Fancelli D, Minutolo F. An update on therapeutic opportunities offered by cancer glycolytic metabolism. Bioorg Med Chem Lett. 2014;24(21):4915–25. https://doi.org/10.1016/j.bmcl.2014.09.041.CrossRefPubMed

142.

Wang TA, Zhang XD, Guo XY, Xian SL, Lu YF. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth. Oncol Rep. 2016;35(3):1287–96.

143.

Guo X, Zhang X, Wang T, Xian S, Lu Y. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway. Biochem Biophys Res Commun. 2016;475(1):37–43. https://doi.org/10.1016/j.bbrc.2016.04.151.CrossRefPubMed

144.

Sun L, Yin Y, Clark LH, Sun W, Sullivan SA, Tran AQ, et al. Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer. Oncotarget. 2017;8(38):63551–61. https://doi.org/10.18632/oncotarget.18854.CrossRefPubMedPubMedCentral

145.

Chen R, Lai LA, Sullivan Y, Wong M, Wang L, Riddell J, et al. Disrupting glutamine metabolic pathways to sensitize gemcitabine-resistant pancreatic cancer. Sci Rep. 2017;7(1):7950. https://doi.org/10.1038/s41598-017-08436-6.CrossRefPubMedPubMedCentral

146.

Cervantes-Madrid D, Dominguez-Gomez G, Gonzalez-Fierro A, Perez-Cardenas E, Taja-Chayeb L, Trejo-Becerril C, et al. Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6-diazo-5-oxo-L-norleucine and orlistat in colon cancer. Oncol Lett. 2017;13(3):1905–10. https://doi.org/10.3892/ol.2017.5615.CrossRefPubMedPubMedCentral

147.

Korangath P, Teo WW, Sadik H, Han L, Mori N, Huijts CM, et al. Targeting glutamine metabolism in breast cancer with aminooxyacetate. Clin Cancer Res. 2015;21(14):3263–73. https://doi.org/10.1158/1078-0432.Ccr-14-1200.CrossRefPubMedPubMedCentral

148.

Coni S, Di Magno L, Serrao SM, Kanamori Y, Agostinelli E, Canettieri G. Polyamine metabolism as a therapeutic target in Hedgehog-driven basal cell carcinoma and medulloblastoma. Cells. 2019;8(2):150. https://doi.org/10.3390/cells8020150.CrossRefPubMedCentral

149.

Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic Instruction of Immunity. Cell. 2017;169(4):570–86. https://doi.org/10.1016/j.cell.2017.04.004.CrossRefPubMedPubMedCentral

150.

Patel CH, Powell JD. Targeting T cell metabolism to regulate T cell activation, differentiation and function in disease. Curr Opin Immunol. 2017;46:82–8. https://doi.org/10.1016/j.coi.2017.04.006.CrossRefPubMedPubMedCentral

151.

Ma EH, Poffenberger MC, Wong AH, Jones RG. The role of AMPK in T cell metabolism and function. Curr Opin Immunol. 2017;46:45–52. https://doi.org/10.1016/j.coi.2017.04.004.CrossRefPubMed

152.

Cluxton D, Petrasca A, Moran B, Fletcher JM. Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis. Front Immunol. 2019;10:115. https://doi.org/10.3389/fimmu.2019.00115.CrossRefPubMedPubMedCentral

153.

Young KE, Flaherty S, Woodman KM, Sharma-Walia N, Reynolds JM. Fatty acid synthase regulates the pathogenicity of Th17 cells. J Leukoc Biol. 2017;102(5):1229–35. https://doi.org/10.1189/jlb.3AB0417-159RR.CrossRefPubMedPubMedCentral

154.

Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, et al. Bile acid metabolites control T(H)17 and T(reg) cell differentiation. Nature. 2019;576(7785):143–8. https://doi.org/10.1038/s41586-019-1785-z.CrossRefPubMedPubMedCentral

155.

Sun L, Fu J, Zhou Y. Metabolism Controls the Balance of Th17/T-Regulatory Cells. Front Immunol. 2017;8:1632. https://doi.org/10.3389/fimmu.2017.01632.CrossRefPubMedPubMedCentral

156.

Leone RD, Emens LA. Targeting adenosine for cancer immunotherapy. J Immunother Cancer. 2018;6(1):57. https://doi.org/10.1186/s40425-018-0360-8.CrossRefPubMedPubMedCentral

157.

Giannone G, Ghisoni E, Genta S, Scotto G, Tuninetti V, Turinetto M, et al. Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy. Int J Mol Sci. 2020;21(12):4414. https://doi.org/10.3390/ijms21124414.CrossRefPubMedCentral

Titel: Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy
verfasst von: Yin Qianmei
Su Zehong
Wang Guang
Li Hui
Gaojian Lian
Publikationsdatum: 24.07.2021
Verlag: Springer US
Erschienen in: Immunologic Research / Ausgabe 5/2021
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-021-09211-6

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Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy

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