<42> Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
Anticancer immunotherapy by CTLA-4 blockaderelies on the gut microbiota
M Vétizou et al. Science.
2015 Nov 27; 350(6264):1079-84.
Speaker: Yu-Ting Shao (邵郁婷) Time:14:00~15:00,May.31,2017
Commentator: Bei-Chang Yang,Ph.D. (楊倍昌教授) Place: Room 601
Blockade of cytotoxic T-lymphocyte antigen(CTLA-4) by Antibodies have been successfully used as cancer immunotherapy. Ipilimumab is a fully human monoclonal antibody directed against CTLA-4. However, blockade of CTLA-4 by ipilimumab often results in immune-related adverse events (irAEs),including diarrhea and enterocolitis.A randomized study has suggested that a contributing factor to enterocolitis may be intestinal microflora and bacterial antigens. They find that the anti-tumor 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.It 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. Suggest that the efficacy of CTLA-4 blockade is influenced by Bacteroides species.
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