Dietary intervention through bacterial-derived butyrate elicits anti-tumor activity and increases anti-PD-1 response.

Fiche publication

Date publication

décembre 2026

Journal

Gut microbes

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain , Mme TRUNTZER Caroline

Tous les auteurs :
Benlaïfaoui M, Richard C, Hunter S, Méndez-Salazar EO, Kourtian S, Malo J, Prifti DK, Ponce M, Khalfi S, Belkaïd W, Messaoudene M, Boidot R, Truntzer C, Girhinghelli F, Lehoux-Duboix C, Ancuta P, Elkrief A, Marcil V, Routy B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42454784

Résumé

The gut microbiome is increasingly recognized as a key modulator of cancer immunotherapy efficacy. Given that diet is one of the most important determinants of the gut microbiome composition and function, nutritional strategies have emerged as promising tools to modulate anti-tumor immune responses. Here, we demonstrate that dietary supplementation with inulin reduces tumor growth and enhances PD-1 efficacy in mice. These effects were associated with increased frequencies of intra-tumoral CD8⁺ and CD4⁺ T cells, particularly CCR9⁺CXCR3⁺ subsets, and enrichment of beneficial taxa such as and , alongside elevated short-chain fatty acids (SCFA) levels. Among the SCFA, butyrate alone recapitulated the anti-tumor effect of inulin and had an additive effect when combined with PD-1 therapy in a CD8⁺ T cell-dependent manner. Butyrate exerted its anti-tumor effects by transcriptional changes in CD8⁺ T cells involving activation of proliferation, trafficking, and metabolic pathways. In a cohort of 117 non-small cell lung cancer (NSCLC) patients amenable to immunotherapy, the median dietary fiber intake was lower than previously published studies but correlated with enrichment of and metabolic pathways related to sucrose degradation and tryptophan biosynthesis. Collectively, our findings highlight the therapeutic potential of targeting diet-microbiome-immune system interactions to improve cancer immunotherapy outcomes.