Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota Academic Article uri icon

Overview

MeSH Major

  • Antibodies, Monoclonal
  • Bacteroides
  • CTLA-4 Antigen
  • Gastrointestinal Microbiome
  • Melanoma
  • Skin Neoplasms

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.

authors

publication date

  • November 27, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4721659

Digital Object Identifier (DOI)

  • 10.1126/science.aad1329

PubMed ID

  • 26541610

Additional Document Info

start page

  • 1079

end page

  • 84

volume

  • 350

number

  • 6264