AI Article Synopsis
- Antibodies targeting CTLA-4 have shown effectiveness as cancer immunotherapy, with findings indicating that their antitumor effects are influenced by specific Bacteroides species.
- Research in both mice and patients revealed that a T cell response to B. thetaiotaomicron or B. fragilis is linked to the effectiveness of CTLA-4 blockade therapies.
- In studies, antibiotic treatment or the absence of gut bacteria eliminated the tumor response to CTLA-4 blockade, but this was restored through methods such as administering B. fragilis, immunization with its polysaccharides, or transferring specific T cells.
Article 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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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659 | PMC |
| http://dx.doi.org/10.1126/science.aad1329 | DOI Listing |
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