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Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model

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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.

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Abbreviations

RCC:

Renal cell carcinoma

Tregs:

Regulatory T cells

MDSCs:

Myeloid-derived suppressor cells

NK:

Natural killer

Th:

T-helper

IL-2:

Interleukin-2

IL-6:

Interleukin-6

IL-10:

Interleukin-10

IFN-γ:

Interferon-γ

FasL:

Fas ligand

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work is supported by the Nature Science Foundation of Hubei Province of China 302132458.

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Authors and Affiliations

  1. Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China

    Liang Chen, Sixing Yang, Wenbiao Liao & Yunhe Xiong

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  1. Liang Chen
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  2. Sixing Yang
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  3. Wenbiao Liao
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  4. Yunhe Xiong
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Correspondence to Sixing Yang.

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Chen, L., Yang, S., Liao, W. et al. Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model. Cell Biochem Biophys 72, 617–625 (2015). https://doi.org/10.1007/s12013-015-0513-z

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