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Article Dans Une Revue Science Année : 2015

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

Florent Ginhoux

Résumé

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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Dates et versions

hal-02639698 , version 1 (17-03-2021)

Identifiants

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Marie Vétizou, Jonathan M. Pitt, Romain Daillere, Patricia Lepage, Nadine Waldschmitt, et al.. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science, 2015, 350 (6264), pp.1079-1084. ⟨10.1126/science.aad1329⟩. ⟨hal-02639698⟩
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