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ResearchIn-Press PreviewMetabolismOncology Open Access | 10.1172/jci.insight.145207

Ketogenic diet and ketone bodies enhance the anticancer effects of PD1 blockade

Gladys Ferrere,1 Maryam Tidjani Alou,1 Peng Liu,2 Anne-Gaëlle Goubet,1 Marine Fidelle,1 Oliver Kepp,2 Sylvère Durand,2 Valerio Iebba,3 Aurélie Fluckiger,1 Romain Daillère,4 Cassandra Thelemaque,1 Claudia Grajeda-Iglesias,1 Carolina Alves Costa Silva,1 Fanny Aprahamian,2 Deborah Lefevre,2 Liwei Zhao,2 Bernhard Ryffel,7 Emeline Colomba,8 Monica Arnedos,8 Damien Drubay,9 Conrad Rauber,1 Didier Raoult,10 Francesco Asnicar,11 Tim Spector,12 Nicola Segata,11 Lisa Derosa,13 Guido Kroemer,2 and Laurence Zitvogel.1

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Fidelle, M. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Durand, S. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Iebba, V. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Fluckiger, A. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Daillère, R. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Thelemaque, C. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Grajeda-Iglesias, C. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Alves Costa Silva, C. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Aprahamian, F. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Lefevre, D. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Zhao, L. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Ryffel, B. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Colomba, E. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Arnedos, M. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Drubay, D. in: JCI | PubMed | Google Scholar |

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

Find articles by Rauber, C. in: JCI | PubMed | Google Scholar

1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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1Institut Gustave Roussy, INSERM U1015, Villejuif, France

2Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Paris, France

3Department of Medical Sciences, University of Trieste, Trieste, Italy

4EverImmune, Villejuif, France

5Institut Gustave Roussy, INSERM U1015, France, France

6Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Villejuif, France

7INEM - UMR7355, CNRS and University Orleans, Orleans, France

8Department of Oncology, Gustave Roussy Hospital, Villejuif, France

9Institut Gustave Roussy, Department of Biostatistics and Epidemiology, University Paris-Saclay, Villejuif, France

10URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU-Méditerranée Infection, Marseille, France

11Department Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

12The Department of Twin Research & Genetic Epidemiology, King’s College London, London, United Kingdom

13Institute Gustave Roussy, INSERM U1015, Villejuif, France

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Published December 15, 2020 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.145207.
Copyright © 2020, Ferrere et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 15, 2020 - Version history
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Abstract

Limited experimental evidence bridges nutrition and cancer immunosurveillance. Here, we show that ketogenic diet (KD) or its principal ketone body, 3-hydroxybutyrate (3HB), most specifically in an intermittent scheduling, induced T cell-dependent tumor growth retardation of aggressive tumor models. In conditions in which anti-PD-1, alone or in combination with anti-CTLA-4, failed to reduce tumor growth in mice receiving a standard diet, KD or oral supplementation of 3HB reestablished therapeutic responses. Supplementation of KD with sucrose (which breaks ketogenesis, abolishing 3HB production) or with a pharmacological antagonist of the 3HB receptor GPR109A abolished the antitumor effects. Mechanistically, 3HB prevented the ICB-linked upregulation of PD-L1 on myeloid cells while favoring the expansion of CXCR3+ T cells. KD induced compositional changes of the gut microbiota with distinct species such as Eisenbergiella massiliensis commonly emerging in mice and humans subjected to carbohydrate low diet interventions and highly correlating with serum concentrations of 3HB. Altogether, these results demonstrate that KD induces a 3HB-mediated antineoplastic effect that relies on T-cell mediated cancer immunosurveillance.

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