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The gut microbiota influences anticancer immunosurveillance and general health

Nature Reviews Clinical Oncology volume 15, pages 382–396 (2018)Cite this article

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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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Author notes

  1. These authors contributed equally: Bertrand Routy, Vancheswaran Gopalakrishnan.

Authors and Affiliations

  1. Gustave Roussy Cancer Campus (GRCC), Villejuif, France

    Bertrand Routy, Romain Daillère & Laurence Zitvogel

  2. Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, Villejuif, France

    Bertrand Routy, Romain Daillère & Laurence Zitvogel

  3. Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France

    Bertrand Routy, Romain Daillère & Laurence Zitvogel

  4. University Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France

    Bertrand Routy, Romain Daillère & Laurence Zitvogel

  5. Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Bertrand Routy

  6. Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada

    Bertrand Routy

  7. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Vancheswaran Gopalakrishnan

  8. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France

    Laurence Zitvogel

  9. Department of Surgical Oncology and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jennifer A. Wargo

  10. Metabolomics and Cell Biology Platforms, GRCC, Villejuif, France

    Guido Kroemer

  11. Paris Descartes University, Sorbonne Paris Cité, Paris, France

    Guido Kroemer

  12. Equipe 11 Labellisée-Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France

    Guido Kroemer

  13. Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France

    Guido Kroemer

  14. Institut National de la Santé et de la Recherche Médicale (INSERM) U1138, Paris, France

    Guido Kroemer

  15. Pierre et Marie Curie University, Paris, France

    Guido Kroemer

  16. Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France

    Guido Kroemer

  17. Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden

    Guido Kroemer

Authors
  1. Bertrand Routy
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  2. Vancheswaran Gopalakrishnan
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  3. Romain Daillère
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  4. Laurence Zitvogel
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Contributions

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.

Corresponding author

Correspondence to Guido Kroemer.

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Competing interests

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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