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Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

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Vétizou, Marie | Pitt, Jonathan M. | Daillere, Romain | Lepage, Patricia | Waldschmitt, Nadine | Flament, Caroline | Rusakiewicz, Sylvie | Routy, Bertrand | Roberti, Maria P. | Duong, Connie P. M. | Poirier-Colame, Vichnou | Roux, Antoine | Becharef, Sonia | Formenti, Silvia | Golden, Encouse | Cording, Sascha | Eberl, Gerard | Schlitzer, Andreas | Ginhoux, Florent | Mani, Sridhar | Yamazaki, Takahiro | Jacquelot, Nicolas | Enot, David P. | Bérard, Marion | Nigou, Jérôme | Opolon, Paule | Eggermont, Alexander | Woerther, Paul-Louis | Chachaty, Elisabeth | Chaput, Nathalie | Robert, Caroline | Mateus, Christina | Kroemer, Guido | Raoult, Didier | Boneca, Ivo Gomperts | Carbonnel, Franck | Chamaillard, Mathias | Zitvogel, Laurence

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, Tcell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

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