Open AccessNeutrophils suppress tumor‐infiltrating T cells in colon cancer via matrix metalloproteinase‐mediated activation of TGF β
Author(s) -
Germann Markus,
Zangger Nadine,
Sauvain MarcOlivier,
Sempoux Christine,
Bowler Amber D,
Wirapati Pratyaksha,
Kandalaft Lana E,
Delorenzi Mauro,
Tejpar Sabine,
Coukos George,
Radtke Freddy
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201910681
Subject(s) - cancer research , tumor microenvironment , immunotherapy , colorectal cancer , t cell , cancer immunotherapy , in vivo , infiltration (hvac) , cell , immunology , matrix metalloproteinase , biology , chemistry , cancer , medicine , immune system , tumor cells , physics , genetics , microbiology and biotechnology , thermodynamics
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 TGF β. CRC patient neutrophils similarly suppressed T cells via TGF β in vitro, and public gene expression datasets suggested that T‐cell activity is lowest in CRC s with combined neutrophil infiltration and TGF β activation. Thus, the interaction of neutrophils with a TGF β‐rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC .