Resveratrol induces the suppression of tumor-derived CD4⁺CD25⁺ regulatory T cells

CD4⁺CD25⁺ regulatory T cells (Treg cells) are negative regulator of the immune system and main obstacles to cancer immunotherapy in tumor-bearing hosts. Resveratrol is a natural product found in grapes with both immunomodulatory and anticancer effects, which can be controlled by Treg cells. Therefore, to determine whether resveratrol performs these actions via Treg cells, we investigated changes in Treg cell population and immunomodulatory cytokines in EG7 tumor-bearing C57BL/6 mice. In the present study, CD4⁺CD25⁺ cell population among CD4⁺ cells was inhibited ex vivo by resveratrol treatment in a dose-dependent manner. FoxP3⁺ expressing cells among CD4⁺CD25⁺ population were significantly reduced after resveratrol treatment ex vivo in intracellular FACS analysis. Single intraperitoneal administration of 4 mg/kg resveratrol suppressed the CD4⁺CD25⁺ cell population among CD4⁺ cells and downregulated secretion of TGF-β, an immunosuppressive cytokine, measured from the spleens of tumor-bearing mice. Furthermore, resveratrol enhanced IFN-γ expression in CD8⁺ T cells both ex vivo and in vivo, leading to immune stimulation. Taken together, these results suggest that resveratrol has a suppressive role on CD4⁺CD25⁺ cell population and makes peritumoral microenvironment unfavorable to tumor in tumor-bearing mice. Thus, resveratrol can be considered as possible adjuvant material for vaccination-based cancer therapy.