Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade.
Level 5 - mechanism / opinion, no new human data
Preclinical animal models and mechanistic laboratory research
PubMed 33320838 · doi:10.1172/jci.insight.145207
What was done
Investigated the effects of a ketogenic diet (KD) and its primary ketone body, 3-hydroxybutyrate (3HB, given intermittently), in aggressive mouse tumor models resistant to anti-PD-1 or anti-CTLA-4 therapy. Researchers assessed tumor growth, evaluated the impact of sucrose co-administration and GPR109A receptor pharmacological antagonism, examined immune cell phenotypes (myeloid PD-L1 expression and CXCR3+ T cell expansion), and analyzed gut microbiome changes in mice and human subjects on low-carbohydrate diets.
What was found
The abstract reports qualitative findings without exact numerical values or effect sizes. KD or oral 3HB supplementation restored therapeutic responsiveness to anti-PD-1 and combined anti-PD-1/anti-CTLA-4 therapy and caused T cell-dependent tumor growth retardation. Antitumor efficacy was abolished by sucrose supplementation or GPR109A receptor blockade. Mechanistically, 3HB prevented checkpoint inhibitor-induced PD-L1 upregulation on myeloid cells and expanded CXCR3+ T cells. Both mice and humans consuming low-carbohydrate diets exhibited shifts in gut microbiota, including increases in Eisenbergiella massiliensis, which correlated with serum 3HB levels.
Why it matters
The study identifies a potential metabolic mechanism by which ketone bodies enhance cancer immunosurveillance and overcome resistance to immune checkpoint blockade in preclinical models.
Limits
The therapeutic findings are derived entirely from mouse tumor models and have not been validated in clinical trials for human cancer immunotherapy. The abstract does not provide sample sizes, tumor types, quantitative effect estimates, or details regarding the human dietary cohort.
Cited by
- supports Published research demonstrates that PD-L1 immune checkpoint inhibitors are greatly augmented in efficacy when combined with a ketogenic diet.