Journal
SCIENCE
Volume 350, Issue 6264, Pages 1079-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aad1329
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Funding
- La Ligue contre le cancer
- ARC
- Ligue Nationale contre le Cancer (Equipes labelisees)
- Agence Nationale pour la Recherche (ANR AUTOPH)
- Agence Nationale pour la Recherche (ANR Emergence)
- European Commission (ArtForce)
- European Research Council
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- Fondation de France
- Canceropole Ile-de-France
- Fondation Bettencourt-Schueller
- Swiss Bridge Foundation
- LabEx Immuno-Oncology
- Institut national du cancer (SIRIC) Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
- NIH [R01 CA161879]
- Fondation pour la Recherche Medicale
- Fondation ARC pour la recherche sur le cancer
- Institut Nationale du Cancer
- Agence Nationale de la Recherche
- BMSI YIG
- SIgN
- Association pour la Recherche contre le Cancer [PGA120140200851]
- INCA-DGOS [GOLD H78008, 2012-1-RT-14-IGR-01]
- [IDPRJNA299112]
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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, Tcell 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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