Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response

In various cancer models, dietary interventions have been shown to inhibit tumor growth, improve anticancer drug efficacy, and enhance immunity, but no such evidence exists for epithelial ovarian cancer (EOC), the most lethal gynecologic cancer. The anticancer immune responses induced by 16-h intermittent fasting (IF) were studied in mice with EOC. IF consistently reduced metabolic growth factors and cytokines that stimulate tumor growth, creating a tumor-hostile environment. Immune profiling showed that IF dramatically alters anti-cancer immunity by increasing CD4(+) and CD8(+) cells, Th1 and cytotoxic responses, and metabolic fitness. beta-hydroxy butyrate (BHB), a bioactive metabolite produced by IF, partially imitates its anticancer effects by inducing CD8(+) effector function. In a direct comparison, IF outperformed exogenous BHB treatment in survival and anti-tumor immune response, probably due to increased ketogenesis. Thus, IF and one of its metabolic mediators BHB suppress EOC growth and sustain a potent antitumor T cell response.