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

M Vétizou, JM Pitt, R Daillère, P Lepage, N Waldschmitt… - Science, 2015 - science.org
M Vétizou, JM Pitt, R Daillère, P Lepage, N Waldschmitt, C Flament, S Rusakiewicz, B Routy
Science, 2015science.org
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 …
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. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
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