Caloric restriction induces macrophage reprogramming and improved epithelial ovarian cancer survival

Abstract Calorie restriction (CR) without malnutrition is a dietary intervention where energy intake reduced by 15 – 40%. The benefits of CR in improving various diseases and extending lifespan has led its investigation cancer. We have reported 30% to limit epithelial ovarian cancer (EOC) progression. Here, we highlight the ability induce immuno-metabolic reprogramming tumor associated macrophages improve EOC survival. Female C57/B6 mice were injected intraperitoneally with 8 × 10 6mouse ID8 (p53 +/+, p53 −/−, or −/−,BRCA1−/−) cells fed ad libitum (RD) subjected CR. Immune profiling was done flow cytometry. Metabolic phenotype determined XF seahorse analyzer. Macrophage marker measured qPCR western blot. Mice on exhibited progression increased overall survival compared RD all models as indicated median survival; p53+/+(65 vs 95 days), p53−/−(50.5 76.5 p53−/−,BRCA1−/−(44 53 days). showed increase antitumor pro-inflammatory (F4/80+CD38+) decrease protumor anti-inflammatory (F4/80+CD206+) macrophages, increasing pro / ratio. Pro-inflammatory intracellular iNOS. change accompanied reprogrammed metabolism glycolysis, reflective macrophages. Decrease resulted robust anti-tumor T cell response. A reprograms macrophage promotes their phenotype, restores immunity resulting growth improved R01 B11209 RR Henry Ford Cancer institute Post Doctorate Fellowship HS