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Targeting the gut and tumor microbiota in cancer

Nature Medicine volume 28, pages 690–703 (2022)Cite this article

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Abstract

Microorganisms within the gut and other niches may contribute to carcinogenesis, as well as shaping cancer immunosurveillance and response to immunotherapy. Our understanding of the complex relationship between different host-intrinsic microorganisms, as well as the multifaceted mechanisms by which they influence health and disease, has grown tremendously—hastening development of novel therapeutic strategies that target the microbiota to improve treatment outcomes in cancer. Accordingly, the evaluation of a patient’s microbial composition and function and its subsequent targeted modulation represent key elements of future multidisciplinary and precision-medicine approaches. In this Review, we outline the current state of research toward harnessing the microbiome to better prevent and treat cancer.

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Fig. 1: Hallmarks of the impact of the gut microbiome on immunity, health and disease.
Fig. 2: Gut oncomicrobiome signatures associated with cancer diagnosis or response to ICB.
Fig. 3: Hallmarks of the impact of tissue-based and tumor-based microorganisms in cancer.
Fig. 4: Personalized approaches incorporate microbiota-centered interventions: a forward-looking view.

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Acknowledgements

The authors thank R. G. Witt, S. Cass, R. Traweek and E. Baruch for their thoughtful input and assistance with preparation of this manuscript. L.Z. and G.K. are supported by Seerave Foundation, the RHU Immunolife, ANR Ileobiome (19-CE15-0029-01), the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR)—Projets blancs; AMMICa (US23/CNRS UMS3655); Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris, ANR-18-IDEX-0001. E.M.P. was supported by the CPRIT Training Award (RP210028).

Author information

Authors and Affiliations

  1. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elizabeth M. Park

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

    Elizabeth M. Park, Manoj Chelvanambi, Neal Bhutiani & Jennifer A. Wargo

  3. Université de Paris, Inserm CIC 1417, I-Reivac, APHP, Hopital Cochin, Paris, France

    Guido Kroemer

  4. Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France

    Guido Kroemer

  5. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France

    Guido Kroemer

  6. Pôle de Biologie, Hôpital Européen George Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France

    Guido Kroemer

  7. Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France

    Laurence Zitvogel

  8. Gustave Roussy, Villejuif, France

    Laurence Zitvogel

  9. Institut National de la Santé et de la Recherche Médicale, UMR1015, Gustave Roussy, Villejuif, France

    Laurence Zitvogel

  10. Center of Clinical Investigations BIOTHERIS, INSERM CIC1428, Gustave Roussy, Villejuif, France

    Laurence Zitvogel

  11. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jennifer A. Wargo

Authors
  1. Elizabeth M. Park
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  2. Manoj Chelvanambi
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  3. Neal Bhutiani
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  4. Guido Kroemer
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  5. Laurence Zitvogel
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  6. Jennifer A. Wargo
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Contributions

All authors contributed equally to the design, preparation and review of this manuscript. J.A.W. supervised and oversaw all aspects of this work.

Corresponding author

Correspondence to Jennifer A. Wargo.

Ethics declarations

Competing interests

J.A.W. is an inventor on a US patent application (PCT/US17/53.717); reports compensation for speaker’s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, MedImmune and Bristol-Myers Squibb; serves as a consultant/advisory board member for Roche/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Biothera Pharmaceuticals and Micronoma. J.A.W. holds stock options from Micronoma. L.Z. received research contracts from Kaleido, Innovate Pharma and Pilege. G.K. had a research contract with Kaleido. L.Z is and G.K. was among the scientific cofounders of EverImmune, a biotech company devoted to the use of commensal bacteria for the treatment of cancers.

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Nature Medicine thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editor: Karen O’Leary, in collaboration with the Nature Medicine team.

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Park, E.M., Chelvanambi, M., Bhutiani, N. et al. Targeting the gut and tumor microbiota in cancer. Nat Med 28, 690–703 (2022). https://doi.org/10.1038/s41591-022-01779-2

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