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Article Dans Une Revue JCI Insight Année : 2021

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

Peng Liu
Oliver Kepp
Sylvère Durand
Romain Daillère
  • Fonction : Auteur

Résumé

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 tumor models. In conditions in which anti-PD-1 alone or in combination with anti-CTLA-4 failed to reduce tumor growth in mice receiving a standard diet, KD, or oral supplementation of 3HB reestablished therapeutic responses. Supplementation of KD with sucrose (which breaks ketogenesis, abolishing 3HB production) or with a pharmacological antagonist of the 3HB receptor GPR109A abolished the antitumor effects. Mechanistically, 3HB prevented the immune checkpoint blockade-linked upregulation of PD-L1 on myeloid cells, while favoring the expansion of CXCR3+ T cells. KD induced compositional changes of the gut microbiota, with distinct species such as Eisenbergiella massiliensis commonly emerging in mice and humans subjected to carbohydrate-low diet interventions and highly correlating with serum concentrations of 3HB. Altogether, these results demonstrate that KD induces a 3HB-mediated antineoplastic effect that relies on T cell-mediated cancer immunosurveillance.
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Origine : Publication financée par une institution

Dates et versions

hal-03169306 , version 1 (15-03-2021)

Identifiants

Citer

Gladys Ferrere, Maryam Tidjani Alou, Peng Liu, Anne-Gaëlle Goubet, Marine Fidelle, et al.. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade. JCI Insight, 2021, 6 (2), ⟨10.1172/jci⟩. ⟨hal-03169306⟩
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