Fiche publication
Date publication
janvier 2022
Journal
Cancer discovery
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain
,
Pr GHIRINGHELLI François
Tous les auteurs :
Messaoudene M, Pidgeon R, Richard C, Ponce M, Diop K, Benlaifaoui M, Nolin-Lapalme A, Cauchois F, Malo J, Belkaid W, Isnard S, Fradet Y, Dridi L, Velin D, Oster P, Raoult D, Ghiringhelli F, Boidot R, Chevrier S, Kysela DT, Brun YV, Falcone EL, Pilon G, Plaza Onate F, Gitton-Quent O, Le Chatelier E, Durand S, Kroemer G, Elkrief A, Marette A, Castagner B, Routy B
Lien Pubmed
Résumé
Several approaches to manipulate the gut microbiome for improving the activity of cancer immune checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC, Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/Foxp3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.
Référence
Cancer Discov. 2022 Jan 14;:
