Resveratrol induces immunogenic cell death of human and murine ovarian carcinoma cells

PURPOSE: This study aimed to clarify whether immunogenic cell death (ICD) contributed to the anti-tumor action of resveratrol against ovarian carcinoma. METHODS: Resveratrol suppressed cell proliferation and induced apoptosis in ovarian carcinoma cells. In addition, resveratrol treatment stimulated cell surface exposure of calreticulin, HMGB1 secretion and ATP release. RESULTS: Vaccination with resveratrol-pretreated ID8 cells significantly inhibited growth of subsequent inoculated xenograft tumor. Direct administration with resveratrol suppressed tumor progression accompanied with compromised cell proliferation and enhanced cell apoptosis. We further characterized increases of both mature dendritic cells and cytotoxic T cells in xenograft tumor in response to resveratrol treatment, which also inhibited TGF-β production and stimulated both IL12p7 and IFN-γ secretion. Most importantly, we demonstrated that combination with PD-1 antibody greatly inhibited tumor growth, while depletion of CD8+ T cells by neutralizing antibody restored xenograft progression. CONCLUSION: Our data suggested resveratrol exerted anti-tumor action against ovarian cancer via both apoptosis and ICD pathways.