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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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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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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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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 Spector, T. 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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Segata, N.
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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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Derosa, L.
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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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Kroemer, G.
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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
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.