OPINION

The gut microbiota influences anticancer immunosurveillance and general health

Abstract

Discoveries made in the past 5 years indicate that the composition of the intestinal microbiota has a major influence on the effectiveness of anticancer immunosurveillance and thereby contributes to the therapeutic activity of immune-checkpoint inhibitors that target cytotoxic T lymphocyte protein 4 (CTLA-4) or the programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) axis, as well as the activity of immunogenic chemotherapies. Herein, we highlight some of the bacteria, such as Akkermansia muciniphila, Bacteroides fragilis, Bifidobacterium spp. and Faecalibacterium spp., that have been associated with favourable anticancer immune responses in both preclinical tumour models and patients with cancer. Importantly, these bacteria also seem to have a positive influence on general health, thus reducing the incidence of metabolic disorders and a wide range of chronic inflammatory pathologies. We surmise that a diverse and propitious microbial ecosystem favours organismal homeostasis, particularly at the level of the cancer–immune dialogue.

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Fig. 1: Investigating correlations between the clinical efficacy of immune-checkpoint blockade and microbiota composition using faecal microbial transplantation in avatar mouse models.
Fig. 2: Potential immune mechanisms linking commensal bacterial species to the anticancer efficacy of immune-checkpoint blockade in preclinical models and patients.

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Acknowledgements

The work of B.R. has been supported by the Gustave Roussy Course of Excellence in Oncology — Fondation Philanthropia and the RK Smiley Canadian Hematology Society. The work of L.Z. and G.K. has been supported by the Ligue contre le Cancer (équipe labellisée); the Agence Nationale de la Recherche (ANR) — Projets Blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la Recherche sur le Cancer (ARC); Cancéropôle Ile-de-France; a donation by Elior; the European Commission (ARTFORCE); the Fondation pour la Recherche Médicale (FRM); the European Research Council (ERC); the Fondation Carrefour; INSERM (HTE); the Institut National du Cancer (INCa); the Institut Universitaire de France; the Leducq Foundation; the LabEx Immuno-Oncology; the Paris Alliance of Cancer Research Institutes (PACRI); the RHU Torino Lumière; the Searave Foundation; the SIRIC (Centre de recherche de l’Institut Curie) Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and philanthropia (from E. Badinter and N. Meyer). The work of J.A.W. is supported by the Binational Science Foundation, an Institutional Research Grant, the generous philanthropic contributions to the University of Texas MD Anderson Melanoma Moon Shot Program, the Melanoma Research Alliance, a Multidisciplinary Research Program Grant, and Stand Up To Cancer. J.A.W. is member of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center.

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B.R., V.G., L.Z., and G.K. researched data for article, made substantial contributions to discussions of content, and wrote the manuscript. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Guido Kroemer.

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L.Z., G.K., and R.D. are founders of everImmune, a biotech company that develops microbial agents for the treatment of cancer. The other authors declare no competing interests.

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Routy, B., Gopalakrishnan, V., Daillère, R. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat Rev Clin Oncol 15, 382–396 (2018). https://doi.org/10.1038/s41571-018-0006-2

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