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

Author:

Routy Bertrand123ORCID,Le Chatelier Emmanuelle4ORCID,Derosa Lisa123,Duong Connie P. M.125ORCID,Alou Maryam Tidjani123,Daillère Romain123ORCID,Fluckiger Aurélie125ORCID,Messaoudene Meriem12,Rauber Conrad123,Roberti Maria P.125,Fidelle Marine135,Flament Caroline125,Poirier-Colame Vichnou125,Opolon Paule6,Klein Christophe7,Iribarren Kristina89101112ORCID,Mondragón Laura89101112ORCID,Jacquelot Nicolas123ORCID,Qu Bo123ORCID,Ferrere Gladys123,Clémenson Céline113,Mezquita Laura114,Masip Jordi Remon114ORCID,Naltet Charles15,Brosseau Solenn15,Kaderbhai Coureche16,Richard Corentin16,Rizvi Hira17,Levenez Florence4,Galleron Nathalie4,Quinquis Benoit4,Pons Nicolas4ORCID,Ryffel Bernhard18,Minard-Colin Véronique119,Gonin Patrick120ORCID,Soria Jean-Charles114,Deutsch Eric113ORCID,Loriot Yohann1314,Ghiringhelli François16,Zalcman Gérard15ORCID,Goldwasser François92122,Escudier Bernard11423ORCID,Hellmann Matthew D.2425ORCID,Eggermont Alexander1214ORCID,Raoult Didier26,Albiges Laurence1314,Kroemer Guido89101112ORCID,Zitvogel Laurence1235ORCID

Affiliation:

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

2. Institut National de la Santé et de la Recherche Medicale (INSERM) U1015 and Equipe Labellisée–Ligue Nationale contre le Cancer, Villejuif, France.

3. Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France.

4. MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy-en-Josas, France.

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

6. Gustave Roussy, Laboratoire de Pathologie Expérimentale, 94800 Villejuif, France.

7. Centre de Recherche des Cordeliers, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Université Pierre et Marie Curie Université Paris 06, Sorbonne Universités, Paris, France.

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

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

10. Equipe 11 Labellisée–Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.

11. INSERM U1138, Paris, France.

12. Université Pierre et Marie Curie, Paris, France.

13. Department of Radiation Oncology, INSERM U1030, and Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France.

14. Department of Medical Oncology, Gustave Roussy, Villejuif, France.

15. Thoracic Oncology Department–CIC1425/CLIP2 Paris-Nord, Hospital Bichat-Claude Bernard, AP-HP, Université Paris-Diderot, Paris, France.

16. Department of Medical Oncology, Center GF Leclerc, Dijon, France.

17. Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

18. Molecular Immunology and Embryology, UMR 7355, CNRS, University of Orleans, Orléans, France.

19. Department of Pediatric Oncology, GRCC, Villejuif, France.

20. Preclinical Research Platform, GRCC, Villejuif, France.

21. Department of Medical Oncology, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France.

22. Immunomodulatory Therapies Multidisciplinary Study Group (CERTIM), Paris, France.

23. INSERM U981, GRCC, Villejuif, France.

24. Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

25. Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

26. URMITE, Aix Marseille Université, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU–Méditerranée Infection, 13005 Marseille, France.

Abstract

Good bacteria help fight cancer Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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