Journal article
Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.
- Germann M Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- Zangger N Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- Sauvain MO Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Sempoux C Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
- Bowler AD Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- Wirapati P Bioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
- Kandalaft LE Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Delorenzi M Bioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
- Tejpar S Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium.
- Coukos G Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Radtke F Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- 2019-12-04
Published in:
- EMBO molecular medicine. - 2020
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.15252/emmm.201910681
- PMID 31793740
- Persistent URL
- https://sonar.ch/global/documents/85921
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