Germann, MarkusZangger, NadineSauvain, Marc-OlivierSempoux, ChristineBowler, Amber D.Wirapati, PratyakshaKandalaft, Lana E.Delorenzi, MauroTejpar, SabineCoukos, GeorgeRadtke, Freddy2019-12-122019-12-122019-12-12202010.15252/emmm.201910681https://infoscience.epfl.ch/handle/20.500.14299/163966WOS:000499796400001WOS:000506587000007High 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 beta. CRC patient neutrophils similarly suppressed T cells via TGF beta in vitro, and public gene expression datasets suggested that T-cell activity is lowest in CRCs with combined neutrophil infiltration and TGF beta activation. Thus, the interaction of neutrophils with a TGF beta-rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC.Medicine, Research & ExperimentalResearch & Experimental Medicinecolorectal cancerneutrophilst-cell suppressiontgf-betatumor microenvironmentpoor-prognosis subtypescolorectal-cancermicroenvironmentinflammationimmunoscoreexclusionblockadeimmunitypd-l1text::journal::journal article::research article