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Can we harness the microbiota to enhance the efficacy of cancer immunotherapy?

Abstract

There is currently much interest in defining how the microbiota shapes immune responses in the context of cancer. Various studies in both mice and humans have associated particular commensal species with better (or worse) outcomes in different cancer types and following treatment with cancer immunotherapies. However, the mechanisms involved remain ill-defined and even controversial. In this Viewpoint, Nature Reviews Immunology has invited six eminent scientists in the field to share their thoughts on the key questions and challenges for the field.

The contributors

B. Brett Finlay is a professor in the Michael Smith Laboratories at the University of British Columbia. His research interests are focused on host–microorganism interactions, at the molecular level, and he has published more than 500 articles. He is a co-author of the books Let Them Eat Dirt and The Whole-Body Microbiome.

Romina Goldszmid is an Earl Stadtman Investigator and Head of the Inflammatory Cell Dynamics Section in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, National Institutes of Health (NIH). She received her PhD degree from the University of Buenos Aires, Argentina, and completed her postdoctoral training at the National Institute of Allergy and Infectious Diseases, NIH. She has a long-standing interest in understanding myeloid cell development, differentiation and function in the context of cancer and infections. Current work in her laboratory aims to dissect the myeloid cell repertoire within tumours, determine their contribution to therapy efficacy and unravel the mechanisms by which the microbiota regulates their function.

Kenya Honda is a professor at Keio University School of Medicine and a team leader at the RIKEN Center for Integrative Medical Sciences, Japan. His laboratory has been aiming to elucidate and translate the mutualistic relationship between the gut microbiota and the host immune system using gnotobiotic animal models.

Giorgio Trinchieri is an NIH Distinguished Investigator and Chief of the Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, NIH. His research has focused for many years on the interplay between inflammation, innate resistance and adaptive immunity and on the role of pro-inflammatory cytokines and interferons in the regulation of haematopoiesis, innate resistance and immunity against infections and tumours. The present focus of his laboratory is on the role of inflammation, innate resistance, immunity and the commensal microbiota in carcinogenesis, cancer progression and prevention of or therapy for cancer.

Jennifer Wargo is a professor of surgical oncology and genomic medicine at the University of Texas MD Anderson Cancer Center. She leads the Program for Innovative Microbiome and Translational Research (PRIME-TR) and is internationally recognized for her contributions to cancer research in immunotherapy and the microbiome.

Laurence Zitvogel, full professor at Paris-Saclay University, is a research director at INSERM and Scientific Director of the immuno-oncology program at Gustave Roussy, France. She has contributed to the field of cancer immunology and immunotherapy, pioneering the concepts of immunogenic cell death and gut microbiota in cancer.

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Acknowledgements

K.H. was funded through AMED LEAP under grant number JP18gm0010003. R.G. is supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute. The L.Z. laboratory is supported by RHU Torino Lumière (ANR-16-RHUS-0008), the ONCOBIOME project (European Union Horizon 2020 programme), the Seerave Foundation, the French Agence Nationale de la Recherche (Ileobiome), the French Ligue Contre le Cancer (Équipe Labelisées programme), the French Association pour la Recherche sur le Cancer, Cancéropôle Ile-de-France, the French Fondation pour la Recherche Médicale, a donation by Elior and Dassault Systems, the European Research Council, Fondation Carrefour, the French Institut National du Cancer INSERM (HTE programme), LabEx Immuno-Oncology, SIRIC Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE) and the CARE network (directed by X. Mariette, Assistance Publique — Hôpitaux de Paris, Kremlin-Bicêtre).

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Correspondence to B. Brett Finlay, Romina Goldszmid, Kenya Honda, Giorgio Trinchieri, Jennifer Wargo or Laurence Zitvogel.

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Competing interests

B.B.F. is a cofounding scientific advisory board member for Vedanta Biosciences. K.H. is a scientific advisory board member of Vedanta Biosciences and 4BIO CAPITAL. J.W. reports compensation and honoraria from Imedex, Dava Oncology, Omniprex, Ilumina, Gilead, PeerView, Physician Education Resource, MedImmune and Bristol-Myers Squibb. J.W. serves as a consultant advisory board member for Roche/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Biothera Pharmaceuticals and Microbiome DX. J.W. also receives research support from GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb and Novartis. J.W. is an adviser and has stock options for Ella Therapeutics. L.Z. is a founder of everImmune, a biotechnology company that develops anticancer probiotics and diagnostic tools to define intestinal dysbiosis in cancer. L.Z. also has an active scientific collaboration (research contract) with Kaleido, Innovate Pharma and Bioaster, which are companies involved in the microbiome space. R.G. and G.T. declare no competing interests.

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Finlay, B.B., Goldszmid, R., Honda, K. et al. Can we harness the microbiota to enhance the efficacy of cancer immunotherapy?. Nat Rev Immunol 20, 522–528 (2020). https://doi.org/10.1038/s41577-020-0374-6

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