Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.
Détails
Télécharger: 31793740.pdf (2669.61 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
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
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
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 14:39
Dernière modification de la notice
17/09/2020 6:10