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Updated: Apr 18, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model
Liang Chen1, Sixing Yang2, Wenbiao Liao1
1Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei, China.
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.
Insights
Resveratrol, a natural compound, inhibits renal cell carcinoma (RCC) growth by boosting CD8(+) T cell activity and enhancing the antitumor immune response within the tumor microenvironment. This suggests potential for RCC immunotherapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- The tumor microenvironment significantly influences the effectiveness of antitumor immune responses in renal cell carcinoma (RCC).
- Resveratrol has demonstrated direct antitumor properties in various cancer models, but its impact on the RCC immune microenvironment remains unexplored.
Purpose of the Study:
- To investigate the immunomodulatory effects of resveratrol on the renal cell carcinoma (RCC) microenvironment.
- To determine if resveratrol can enhance antitumor immunity in RCC models.
Main Methods:
- Administration of low-dose resveratrol to Renca tumor-bearing mice.
- Analysis of immune cell populations (CD8(+) T cells, regulatory T cells, myeloid-derived suppressor cells) within the tumor microenvironment.
- Assessment of cytokine profiles (Th1/Th2 balance, IFN-γ, IL-6, IL-10) and cytotoxicity markers (Fas ligand, Fas).
- Evaluation of angiogenesis markers (vascular endothelial growth factor).
Main Results:
- Low-dose resveratrol inhibited Renca tumor growth, an effect dependent on CD8(+) T cells.
- Resveratrol treatment led to a decrease in regulatory T cells but did not alter myeloid-derived suppressor cells.
- A significant accumulation of activated CD8(+) T cells with enhanced cytotoxicity (increased Fas ligand) was observed.
- Resveratrol shifted the cytokine profile from T-helper (Th) 2 (IL-6, IL-10) towards Th1 (IFN-γ), increasing Fas expression on Renca cells.
- Angiogenesis was downregulated, evidenced by reduced vascular endothelial growth factor levels.
Conclusions:
- Resveratrol modulates the RCC tumor microenvironment by enhancing CD8(+) T cell-mediated antitumor immunity.
- Resveratrol's effects include promoting Th1-biased immunity, increasing T cell cytotoxicity, and reducing angiogenesis.
- These findings suggest resveratrol holds promise as an agent for renal cell carcinoma immunotherapy.
