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Journal Articles Science Year : 2018

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

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Emmanuelle Le Chatelier
Lisa Derosa
Maria Roberti
Marine Fidelle
Gladys Ferrere
Charles Naltet
  • Function : Author
Hira Rizvi
  • Function : Author
Florence F. Levenez
  • Function : Author
Nathalie Galleron
  • Function : Author
Benoit Qu
  • Function : Author
Patrick Gonin
  • Function : Author
  • PersonId : 905950
Charles Soria
  • Function : Author
François Goldwasser
Matthew Hellmann
  • Function : Author

Abstract

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
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Dates and versions

hal-02126484 , version 1 (11-05-2019)

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Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie Duong, Maryam Tidjani Alou, et al.. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 2018, 359 (6371), pp.91-97. ⟨10.1126/science.aan3706⟩. ⟨hal-02126484⟩
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