Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

摘要: Limited experimental evidence bridges nutrition and cancer immunosurveillance. Here, we show that ketogenic diet (KD) - or its principal ketone body, 3-hydroxybutyrate (3HB), most specifically in intermittent scheduling induced T cell-dependent tumor growth retardation of aggressive models. In conditions which anti-PD-1 alone combination with anti-CTLA-4 failed to reduce mice receiving a standard diet, KD, oral supplementation 3HB reestablished therapeutic responses. Supplementation KD sucrose (which breaks ketogenesis, abolishing production) pharmacological antagonist the receptor GPR109A abolished antitumor effects. Mechanistically, prevented immune checkpoint blockade-linked upregulation PD-L1 on myeloid cells, while favoring expansion CXCR3+ cells. compositional changes gut microbiota, distinct species such as Eisenbergiella massiliensis commonly emerging humans subjected carbohydrate-low interventions highly correlating serum concentrations 3HB. Altogether, these results demonstrate induces 3HB-mediated antineoplastic effect relies cell-mediated