Saurer, Leslie; Zysset, Daniel; Rihs, Silvia; Mager, Lukas; Gusberti, Matteo; Simillion, Cedric; Lugli, Alessandro; Zlobec, Inti; Krebs, Philippe; Müller, Christoph (2017). TREM-1 promotes intestinal tumorigenesis. Scientific Reports, 7(1), p. 14870. Nature Publishing Group 10.1038/s41598-017-14516-4
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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses. Increasing evidence suggests a role for TREM-1 not only in acute pathogen-induced reactions but also in chronic and non-infectious inflammatory disorders, including various types of cancer. Here, we demonstrate that genetic deficiency in Trem1 protects from colorectal cancer. In particular, Trem1 (-/-) mice exhibited reduced tumor numbers and load in an experimental model of inflammation-driven tumorigenesis. Gene expression analysis of Trem1 (-/-) versus Trem1 (+/+) tumor tissue demonstrated distinct immune signatures. Whereas Trem1 (-/-) tumors showed an increased abundance of transcripts linked to adaptive immunity, Trem1 (+/+) tumors were characterized by overexpression of innate pro-inflammatory genes associated with tumorigenesis. Compared to adjacent tumor-free colonic mucosa, expression of Trem1 was increased in murine and human colorectal tumors. Unexpectedly, TREM-1 was not detected on tumor-associated Ly6C(-) MHC class II(+) macrophages. In contrast, TREM-1 was highly expressed by tumor-infiltrating neutrophils which represented the predominant myeloid population in Trem1 (+/+) but not in Trem1 (-/-) tumors. Collectively, our findings demonstrate a clear role of TREM-1 for intestinal tumorigenesis and indicate TREM-1-expressing neutrophils as critical players in colorectal tumor development.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit 04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology 04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Saurer, Leslie, Zysset, Daniel, Rihs, Silvia, Mager, Lukas, Zlobec, Inti, Krebs, Philippe, Müller, Christoph (C) |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Christoph Müller |
Date Deposited: |
16 Nov 2017 07:53 |
Last Modified: |
29 Mar 2023 23:35 |
Publisher DOI: |
10.1038/s41598-017-14516-4 |
PubMed ID: |
29093489 |
BORIS DOI: |
10.7892/boris.106850 |
URI: |
https://boris.unibe.ch/id/eprint/106850 |
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