Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_F06A8D6CE8D2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.
Périodique
EMBO molecular medicine
Auteur(s)
Germann M., Zangger N., Sauvain M.O., Sempoux C., Bowler A.D., Wirapati P., Kandalaft L.E., Delorenzi M., Tejpar S., Coukos G., Radtke F.
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Statut éditorial
Publié
Date de publication
09/01/2020
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
e10681
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to achieve broader immunotherapy responsiveness. Here, we investigated T cell-suppressive properties of different myeloid cell types in an inducible colon tumor mouse model. The most potent inhibitors of T-cell activity were tumor-infiltrating neutrophils. Gene expression analysis and combined in vitro and in vivo tests indicated that T-cell suppression is mediated by neutrophil-secreted metalloproteinase activation of latent TGFβ. CRC patient neutrophils similarly suppressed T cells via TGFβ in vitro, and public gene expression datasets suggested that T-cell activity is lowest in CRCs with combined neutrophil infiltration and TGFβ activation. Thus, the interaction of neutrophils with a TGFβ-rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC.
Mots-clé
T-cell suppression, TGF-β, colorectal cancer, neutrophils, tumor microenvironment
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/12/2019 15:39
Dernière modification de la notice
17/09/2020 7:10
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