Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
2015/11/05 by Marie Vétizou, Jonathan M. Pitt, Romain Daillère +45 · 3,445 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Biology #Blockade #CTLA-4 #Cancer immunotherapy #Clostridium difficile and Clostridium perfringens research #Gut flora #Gut microbiota and health #Immune system #Immunology #Immunotherapy #Internal medicine #Medicine #Receptor #T cell #Tryptophan and brain disorders
paper · open access · doi:10.1126/science.aad1329
published in Science 350(6264), 1079-1084 (American Association for the Advancement of Science)
openalex publication_date 2015/11/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Abstract
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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