Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer.

Animals B7-1 Antigen / metabolism B7-2 Antigen / metabolism Biomarkers, Tumor / blood Butyrates / blood CTLA-4 Antigen / antagonists & inhibitors Dendritic Cells / metabolism Fatty Acids, Volatile / blood Gastrointestinal Microbiome / drug effects Humans Ipilimumab / pharmacology Mice Mice, Inbred BALB C Neoplasms / blood Propionates / blood RNA, Ribosomal, 16S / metabolism T-Lymphocytes / drug effects T-Lymphocytes, Regulatory / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 05 2020
Historique:
received: 04 04 2019
accepted: 08 04 2020
entrez: 3 5 2020
pubmed: 3 5 2020
medline: 4 8 2020
Statut: epublish

Résumé

Gut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (SCFA) are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluate in mice and in patients treated with anti-CTLA-4 blocking mAbs whether SCFA levels is related to clinical outcome. High blood butyrate and propionate levels are associated with resistance to CTLA-4 blockade and higher proportion of Treg cells. In mice, butyrate restrains anti-CTLA-4-induced up-regulation of CD80/CD86 on dendritic cells and ICOS on T cells, accumulation of tumor-specific T cells and memory T cells. In patients, high blood butyrate levels moderate ipilimumab-induced accumulation of memory and ICOS + CD4 + T cells and IL-2 impregnation. Altogether, these results suggest that SCFA limits anti-CTLA-4 activity.

Identifiants

DOI: 10.1038/s41467-020-16079-x PMID: 32358520 PMC: PMC7195489
pubmed: 32358520
doi: 10.1038/s41467-020-16079-x
pii: 10.1038/s41467-020-16079-x
pmc: PMC7195489
doi:

Substances chimiques

B7-1 Antigen 0
B7-2 Antigen 0
Biomarkers, Tumor 0
Butyrates 0
CTLA-4 Antigen 0
Fatty Acids, Volatile 0
Ipilimumab 0
Propionates 0
RNA, Ribosomal, 16S 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2168

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Auteurs

Clélia Coutzac (C)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.
Université Paris-Descartes, Faculté de Médicine, F-75006, Paris, France.
Hôpital Européen Georges Pompidou, Département de Gastroentérologie et Oncologie Digestive, Assistance Publique-Hôpitaux de Paris, F-75015, Paris, France.
ORCID: 0000-0002-8347-6957

Jean-Mehdi Jouniaux (JM)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.

Angelo Paci (A)

Université Paris-Saclay, Institut Gustave Roussy, CNRS, Vectorologie et thérapeutiques anticancéreuses, F-94805, Villejuif, France.
Institut Gustave Roussy, Pharmacology and Drug Analysis Department, Villejuif, F-94805, France.
Université Paris-Saclay, Faculté de Pharmacie, Chatenay-Malabry, F-92296, France.
ORCID: 0000-0002-4849-0825

Julien Schmidt (J)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.

Domenico Mallardo (D)

Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Instituto Nazionale Tumori- IRCCS -Fondazione G. Pascale, Napoli, Italia.
ORCID: 0000-0002-1081-5313

Atmane Seck (A)

Université Paris-Saclay, Institut Gustave Roussy, CNRS, Vectorologie et thérapeutiques anticancéreuses, F-94805, Villejuif, France.
Institut Gustave Roussy, Pharmacology and Drug Analysis Department, Villejuif, F-94805, France.

Vahe Asvatourian (V)

Institut Gustave Roussy, Biostatistics and Epidemiology Unit, Villejuif, F-94805, France.
Université Paris-Saclay, UVSQ, Inserm, CESP, 94807, Villejuif, France.

Lydie Cassard (L)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
ORCID: 0000-0001-8373-041X

Patrick Saulnier (P)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Genomic platform Molecular Biopathology unit and Biological Resource Center, F-94805, Villejuif, France.

Ludovic Lacroix (L)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Genomic platform Molecular Biopathology unit and Biological Resource Center, F-94805, Villejuif, France.

Paul-Louis Woerther (PL)

Institut Gustave Roussy, Department of Medical Biology and Pathology, Microbiology unit, Villejuif, F-94805, France.

Aurore Vozy (A)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.

Marie Naigeon (M)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.

Laetitia Nebot-Bral (L)

Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.
Université Paris-Saclay, Institut Gustave Roussy, CNRS, Stabilité génétique et oncogenèse, 94805, Villejuif, France.

Mélanie Desbois (M)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
ORCID: 0000-0001-5503-8821

Ester Simeone (E)

Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Instituto Nazionale Tumori- IRCCS -Fondazione G. Pascale, Napoli, Italia.

Christine Mateus (C)

Institut Gustave Roussy, Dermatology Unit, Department of Medicine, Villejuif, F-94805, France.

Lisa Boselli (L)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.

Jonathan Grivel (J)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.

Emilie Soularue (E)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France.
Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.
Hôpital du Kremlin Bicêtre Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.

Patricia Lepage (P)

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France.
ORCID: 0000-0002-9501-6771

Franck Carbonnel (F)

Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.
Hôpital du Kremlin Bicêtre Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.

Paolo Antonio Ascierto (PA)

Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Instituto Nazionale Tumori- IRCCS -Fondazione G. Pascale, Napoli, Italia.
ORCID: 0000-0002-8322-475X

Caroline Robert (C)

Université Paris-Saclay, Faculté de Médicine, Le Kremlin Bicêtre, F-94276, France.
Institut Gustave Roussy, Dermatology Unit, Department of Medicine, Villejuif, F-94805, France.
ORCID: 0000-0002-9493-0238

Nathalie Chaput (N)

Université Paris-Saclay, Institut Gustave Roussy, Inserm, CNRS, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Laboratoire d'Immunomonitoring en Oncologie, F-94805, Villejuif, France. nathalie.chaput@gustaveroussy.fr.
Université Paris-Saclay, Faculté de Pharmacie, Chatenay-Malabry, F-92296, France. nathalie.chaput@gustaveroussy.fr.
Université Paris-Saclay, Institut Gustave Roussy, CNRS, Stabilité génétique et oncogenèse, 94805, Villejuif, France. nathalie.chaput@gustaveroussy.fr.
ORCID: 0000-0003-3968-8669

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Systemic short chain fatty acids limit...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD80 › Systemic short chain fatty acids limit...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD86 › Systemic short chain fatty acids limit...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Systemic short chain fatty acids limit...
questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Butyrates › Systemic short chain fatty acids limit...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigène CTLA-4 › Systemic short chain fatty acids limit...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Systemic short chain fatty acids limit...
questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Systemic short chain fatty acids limit...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Biodiversité › Biote › Microbiote › Microbiome gastro-intestinal › Systemic short chain fatty acids limit...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Systemic short chain fatty acids limit...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Ipilimumab › Systemic short chain fatty acids limit...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Systemic short chain fatty acids limit...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Systemic short chain fatty acids limit...
questionsmedicales.fr › Tumeurs › Systemic short chain fatty acids limit...
questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Propionates › Systemic short chain fatty acids limit...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN ribosomique › ARN ribosomique 16S › Systemic short chain fatty acids limit...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Systemic short chain fatty acids limit...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T régulateurs › Systemic short chain fatty acids limit...