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

Clélia Coutzac, Jean-Mehdi Jouniaux, Angelo Paci, Julien Schmidt, Domenico Mallardo, Atmane Seck, Vahe Asvatourian, Lydie Cassard, Patrick Saulnier, Ludovic Lacroix, Paul-Louis Woerther, Aurore Vozy, Marie Naigeon, Laetitia Nebot-Bral, Mélanie Desbois, Ester Simeone, Christine Mateus, Lisa Boselli, Jonathan Grivel, Emilie Soularue, Patricia Lepage, Franck Carbonnel, Paolo Antonio Ascierto, Caroline Robert and Nathalie Chaput ()
Additional contact information
Clélia Coutzac: Laboratoire d’Immunomonitoring en Oncologie
Jean-Mehdi Jouniaux: Laboratoire d’Immunomonitoring en Oncologie
Angelo Paci: Vectorologie et thérapeutiques anticancéreuses
Julien Schmidt: Laboratoire d’Immunomonitoring en Oncologie
Domenico Mallardo: Instituto Nazionale Tumori- IRCCS –Fondazione G. Pascale
Atmane Seck: Vectorologie et thérapeutiques anticancéreuses
Vahe Asvatourian: Biostatistics and Epidemiology Unit
Lydie Cassard: Laboratoire d’Immunomonitoring en Oncologie
Patrick Saulnier: Genomic platform Molecular Biopathology unit and Biological Resource Center
Ludovic Lacroix: Genomic platform Molecular Biopathology unit and Biological Resource Center
Paul-Louis Woerther: Microbiology unit
Aurore Vozy: Laboratoire d’Immunomonitoring en Oncologie
Marie Naigeon: Laboratoire d’Immunomonitoring en Oncologie
Laetitia Nebot-Bral: Université Paris-Saclay, Faculté de Médicine
Mélanie Desbois: Laboratoire d’Immunomonitoring en Oncologie
Ester Simeone: Instituto Nazionale Tumori- IRCCS –Fondazione G. Pascale
Christine Mateus: Department of Medicine
Lisa Boselli: Laboratoire d’Immunomonitoring en Oncologie
Jonathan Grivel: Laboratoire d’Immunomonitoring en Oncologie
Emilie Soularue: Laboratoire d’Immunomonitoring en Oncologie
Patricia Lepage: Micalis Institute
Franck Carbonnel: Université Paris-Saclay, Faculté de Médicine
Paolo Antonio Ascierto: Instituto Nazionale Tumori- IRCCS –Fondazione G. Pascale
Caroline Robert: Université Paris-Saclay, Faculté de Médicine
Nathalie Chaput: Laboratoire d’Immunomonitoring en Oncologie

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16079-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16079-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16079-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().