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Original Research

Resveratrol exerts antitumor effects by downregulating CD8+CD122+ Tregs in murine hepatocellular carcinoma

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Article: 1829346 | Received 31 Jan 2020, Accepted 23 Sep 2020, Published online: 24 Oct 2020

References

  • Han Y, Jo H, Cho JH, Dhanasekaran DN, Song YS. Resveratrol as a tumor-suppressive nutraceutical modulating tumor microenvironment and malignant behaviors of cancer. Int J Mol Sci. 2019;20:925. doi:10.3390/ijms20040925.
  • Qian B-Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–13. doi:10.1016/j.cell.2010.03.014.
  • Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013;144:512–527. doi:10.1053/j.gastro.2013.01.002.
  • Paluskievicz CM, Cao X, Abdi R, Zheng P, Liu Y, Bromberg JS. T regulatory cells and priming the suppressive tumor microenvironment. Front Immunol. 2019;10:2453. doi:10.3389/fimmu.2019.02453.
  • Endharti AT, Rifa IM, Shi Z, Fukuoka Y, Nakahara Y, Kawamoto Y, Takeda K, Isobe KI, Suzuki H. Cutting edge: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-gamma production and proliferation of CD8+ T cells. J Immunol. 2005;175:7093–7097. doi:10.4049/jimmunol.175.11.7093.
  • Rifa’i M, Kawamoto Y, Nakashima I, Suzuki H. Essential roles of CD8+CD122+ regulatory T cells in the maintenance of T cell homeostasis. J Exp Med. 2004;200(9):1123–1134. doi:10.1084/jem.20040395.
  • Endharti AT, Okuno Y, Shi Z, Misawa N, Toyokuni S, Ito M,Isobe K-I, Suzuki H. CD8 + CD122 + regulatory T cells (Tregs) and CD4 + tregs cooperatively prevent and cure CD4 + Cell-Induced Colitis. J Immunol. 2011;186(1):41–52. doi:10.4049/jimmunol.1000800.
  • Akane K, Kojima S, Mak TW, Shiku H, Suzuki H. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. Proc Natl Acad Sci U S A. 2016;113:2460–2465. doi:10.1073/pnas.1525098113.
  • Dai Z, Zhang S, Xie Q, Wu S, Su J, Li S, Xu Y, Li XC. Natural CD8+CD122+ T cells are more potent in suppression of allograft rejection than CD4+CD25+ regulatory T cells. Am J Transplant. 2014;14(1):39–48. doi:10.1111/ajt.12515.
  • Molloy MJ, Zhang W, Usherwood EJ. Suppressive CD8+ T cells arise in the absence of CD4 help and compromise control of persistent virus. J Immunol. 2011;186:6218–6226. doi:10.4049/jimmunol.1003812.
  • Wang LX, Li Y, Yang G, Pang PY, Haley D, Walker EB. CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice. Eur J Immunol. 2010;40:1375–1385. doi:10.1002/eji.200839210.
  • Yu P, Steel JC, Zhang M, Morris JC, Waitz R, Fasso M, Allison JP, Waldmann TA. Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model. Proc Natl Acad Sci U S A. 2012;109(16):6187–6192. doi:10.1073/pnas.1203479109.
  • Villarreal DO, Allegrezza MJ, Smith MA, Chin D, Luistro LL, Snyder LA. Targeting of CD122 enhances antitumor immunity by altering the tumor immune environment. Oncotarget. 2017;8(65):109151–109160. doi:10.18632/oncotarget.22642.
  • Yu P, Steel JC, Zhang M, Morris JC, Waldmann TA. Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Cancer Res. 2010;16(24):6019–6028. doi:10.1158/1078-0432.CCR-10-1966.
  • Lafaro KJ, Demirjian AN, Pawlik TM. Epidemiology of hepatocellular carcinoma. Surg Oncol Clin N Am. 2015;24(1):1–17. doi:10.1016/j.soc.2014.09.001.
  • Sakai Y, Honda M, Fujinaga H, Tatsumi I, Mizukoshi E, Nakamoto Y, Kaneko S. Common transcriptional signature of tumor-infiltrating mononuclear inflammatory cells and peripheral blood mononuclear cells in hepatocellular carcinoma patients. Cancer Res. 2008;68(24):10267–10279. doi:10.1158/0008-5472.CAN-08-0911.
  • Zhou J, Ding T, Pan W, Zhu LY, Li L, Zheng L. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int J Cancer. 2009;125:1640–1648. doi:10.1002/ijc.24556.
  • Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, Zhang Z, Yang H, Zhang H, Zhou C. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132(7):2328–2339. doi:10.1053/j.gastro.2007.03.102.
  • Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol. Mutat Res. 2012;750(1):60–82. doi:10.1016/j.mrrev.2011.11.001.
  • Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, et al. The role of resveratrol in cancer therapy. Int J Mol Sci. 2017;18:2589. doi:10.3390/ijms18122589.
  • Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, et al. Caloric restriction mimetics enhance anticancer immunosurveillance. Cancer Cell. 2016;30(1):147–160. doi:10.1016/j.ccell.2016.05.016.
  • Chen L, Yang S, Liao W, Xiong Y. Modification of antitumor immunity and tumor microenvironment by resveratrol in mouse renal tumor model. Cell Biochem Biophys. 2015;72(2):617–625. doi:10.1007/s12013-015-0513-z.
  • Lee-Chang C, Bodogai M, Martin-Montalvo A, Wejksza K, Sanghvi M, Moaddel R, de Cabo R, Biragyn A. Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of tumor-evoked regulatory B cells. J Immunol. 2013;191(8):4141–4151. doi:10.4049/jimmunol.1300606.
  • Yang Y, Paik JH, Cho D, Cho JA, Kim CW. Resveratrol induces the suppression of tumor-derived CD4+CD25+ regulatory T cells. Int Immunopharmacol. 2008;8:542–547. doi:10.1016/j.intimp.2007.12.006.
  • Guan H, Singh NP, Singh UP, Nagarkatti PS, Nagarkatti M. Resveratrol prevents endothelial cells injury in high-dose interleukin-2 therapy against melanoma. PLoS One. 2012;7:e35650. doi:10.1371/journal.pone.0035650.
  • Sun L, Chen B, Jiang R, Li J, Wang B. Resveratrol inhibits lung cancer growth by suppressing M2-like polarization of tumor associated macrophages. Cell Immunol. 2017;311:86–93. doi:10.1016/j.cellimm.2016.11.002.
  • Mukherjee S, Hussaini R, White R, Atwi D, Fried A, Sampat S, Piao L, Pan Q, Banerjee P. TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV plus tumors. Cancer Immunol Immun. 2018;67:761–774. doi:10.1007/s00262-018-2130-3.
  • Gao F, Deng G, Liu W, Zhou K, Li M. Resveratrol suppresses human hepatocellular carcinoma via targeting HGF-c-Met signaling pathway. Oncol Rep. 2017;37(2):1203–1211. doi:10.3892/or.2017.5347.
  • Chai R, Fu H, Zheng Z, Liu T, Ji S, Li G. Resveratrol inhibits proliferation and migration through SIRT1 mediated posttranslational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Mol Med Rep. 2017;16:8037–8044. doi:10.3892/mmr.2017.7612.
  • Zhang B, Yin X, Sui S. Resveratrol inhibited the progression of human hepatocellular carcinoma by inducing autophagy via regulating p53 and the phosphoinositide 3kinase/protein kinase B pathway. Oncol Rep. 2018;40:2758–2765.
  • Bishayee A, Dhir N. Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis. Chem Biol Interact. 2009;179:131–144. doi:10.1016/j.cbi.2008.11.015.
  • Enot DP, Vacchelli E, Jacquelot N, Zitvogel L, Kroemer G. TumGrowth: an open-access web tool for the statistical analysis of tumor growth curves. Oncoimmunology. 2018;7:1462431. doi:10.1080/2162402X.2018.1462431.
  • St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, et al. Genes expressed in human tumor endothelium. Science. 2000;289:1197–1202. doi:10.1126/science.289.5482.1197.
  • Capece D, Fischietti M, Verzella D, Gaggiano A, Cicciarelli G, Tessitore A, Zazzeroni F, Alesse E. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int. 2013;2013:187204. doi:10.1155/2013/187204.
  • Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood. 2007;109:2293–2302. doi:10.1182/blood-2006-02-003988.
  • Wen YJ, Min R, Tricot G, Barlogie B, Yi Q. Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy. Blood. 2002;99:3280–3285. doi:10.1182/blood.V99.9.3280.
  • Zhao F, Korangy F, Greten TF. Cellular immune suppressor mechanisms in patients with hepatocellular carcinoma. Dig Dis. 2012;30(5):477–482. doi:10.1159/000341695.
  • Yan W, Liu X, Ma H, Zhang H, Song X, Gao L, Liang X, Ma C. Tim-3 fosters HCC development by enhancing TGF-beta-mediated alternative activation of macrophages. Gut. 2015;64:1593–1604. doi:10.1136/gutjnl-2014-307671.
  • Tiwari V, Chopra K. Resveratrol prevents alcohol-induced cognitive deficits and brain damage by blocking inflammatory signaling and cell death cascade in neonatal rat brain. J Neurochem. 2011;117:678–690.
  • Rahal K, Schmiedlin-Ren P, Adler J, Dhanani M, Sultani V, Rittershaus AC, Reingold L, Zhu J, McKenna BJ, Christman GM, et al. Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan-polysaccharide rat model of Crohn’s disease. Inflamm Bowel Dis. 2012;18:613–623. doi:10.1002/ibd.21843.
  • Suenaga F, Hatsushika K, Takano S, Ando T, Ohnuma Y, Ogawa H, Nakao A. A possible link between resveratrol and TGF-beta: resveratrol induction of TGF-beta expression and signaling. FEBS Lett. 2008;582:586–590. doi:10.1016/j.febslet.2008.01.024.
  • Serrero G, Lu R. Effect of resveratrol on the expression of autocrine growth modulators in human breast cancer cells. Antioxid Redox Signal. 2001;3:969–979. doi:10.1089/152308601317203512.
  • Rifa’i M, Shi Z, Zhang SY, Lee YH, Shiku H, Isobe KI, Suzuki H. CD8(+)CD122(+) regulatory T cells recognize activated T cells via conventional MHC class I-alpha beta TCR interaction and become IL-10-producing active regulatory cells. Int Immunol. 2008;20:937–947. doi:10.1093/intimm/dxn052.
  • Lin CC, Chin YT, Shih YJ, Chen YR, Chung YY, Lin CY, Hsiung CN, Whang-Peng J, Lee SY,  Lin HY, et al. Resveratrol antagonizes thyroid hormone-induced expression of checkpoint and proliferative genes in oral cancer cells. J Dent Sci. 2019;14:255–262. doi:10.1016/j.jds.2019.01.013.
  • Verdura S, Cuyas E, Cortada E, Brunet J, Lopez-Bonet E, Martin-Castillo B, Bosch-Barrera J, Encinar JA, Menendez JA. Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity. Aging (Albany NY). 2020;12(1):8–34. doi:10.18632/aging.102646.
  • He G, Karin M. NF-kappaB and STAT3 - key players in liver inflammation and cancer. Cell Res. 2011;21:159–168. doi:10.1038/cr.2010.183.
  • Kotha A, Sekharam M, Cilenti L, Siddiquee K, Khaled A, Zervos AS, Carter B, Turkson J, Jove R. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein. Mol Cancer Ther. 2006;5(3):621–629. doi:10.1158/1535-7163.MCT-05-0268.
  • Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR. The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011;121:2723–2735. doi:10.1172/JCI44745.
  • Tu SP, Jin H, Shi JD, Zhu LM, Suo Y, Lu G, Liu A, Wang TC, Yang CS. Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth. Cancer Prev Res (Phila). 2012;5(2):205–215. doi:10.1158/1940-6207.CAPR-11-0247.
  • Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S,Niu G, Kay H, Mulé J, Kerr WG, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005;11(12):1314–1321. doi:10.1038/nm1325.