articleJCI InsightDec 15, 2020GOLD OA

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

GFGladys FerrereMTMaryam Tidjani AlouPLPeng LiuAGAnne‐Gaëlle GoubetMFMarine Fidelle

Inserm · Institut Gustave Roussy · +16 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

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…

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506
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38.96
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100%
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Authors

28

Topics & keywords

Topics
Keywords
  • Immunosurveillance
  • Ketogenesis
  • Ketogenic diet
  • Ketone bodies
  • Blockade
  • Immune checkpoint
  • Cancer research
  • Downregulation and upregulation
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