title: Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model.
abstract: Renal cell carcinoma (RCC) microenvironment plays critical roles in antitumor immune response. Resveratrol exhibits a direct antitumor effect in various tumor models. However, the immunomodulatory effect of resveratrol on RCC microenvironment is unknown. In this study, we found that administration of low dose of resveratrol inhibits Renca tumor growth and its inhibition effect depends on CD8(+) T cells. Moreover, the proportion of regulatory T cells is decreased, while the proportion of myeloid-derived suppressor cells does not alter after resveratrol treatment. More importantly, massive amount of activated CD8(+) T cells accumulates in tumor microenvironment in the resveratrol-treated group and shows increased cytotoxicity, as indicated by a higher expression of Fas ligand. We also found that resveratrol switches the expression of T-helper (Th) 2 cytokines such as interleukin (IL)-6 and IL-10 to Th 1 cytokines with dominance of interferon (IFN)-γ, which increases the expression of Fas in Renca cells. Furthermore, we found resveratrol down-regulates angiogenesis along with decreased level of vascular endothelial growth factor in tumor microenvironment. Our results strongly suggest that resveratrol might be used for RCC immunotherapy through modulating tumor microenvironment.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China. sixingyang2013@163.com.
authors.forename: Sixing
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China.
authors.forename: Wenbiao
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D007155:Immunologic Factors; D015850:Interleukin-6; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D007371:Interferon-gamma; D000077185:Resveratrol
keywords: CD8+ T cells; Cytokine; Fas; Fas ligand; Renal cell carcinoma; Resveratrol; Tumor microenvironment