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

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, T cell 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.…

• EC
  European Commission
• AN
  Agence Nationale de la Recherche
• FP
  Fondation pour la Recherche Médicale
• LC
  Ligue Contre le Cancer
• FD
  Fondation de France
• IN
  Institut National Du Cancer
• IG
  Institut Gustave-Roussy
• SB
  Swiss Bridge Foundation