Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.
Details
Serval ID
serval:BIB_F06A8D6CE8D2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.
Journal
EMBO molecular medicine
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Publication state
Published
Issued date
09/01/2020
Peer-reviewed
Oui
Volume
12
Number
1
Pages
e10681
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
T-cell suppression, TGF-β, colorectal cancer, neutrophils, tumor microenvironment
Pubmed
Web of science
Open Access
Yes
Create date
04/12/2019 14:39
Last modification date
17/09/2020 6:10