ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer

Menche C, Schuhwerk H, Armstark I, Gupta P, Fuchs K, van Roey R, Mosa MH, Hartebrodt A, Hajjaj Y, Clavel Ezquerra A, Selvaraju MK, Geppert CI, Bärthel S, Saur D, Greten FR, Brabletz S, Blumenthal DB, Weigert A, Brabletz T, Farin HF, Stemmler MP (2024)

Publication Type: Journal article

Publication year: 2024

Journal

EMBO Reports EMBO Press

DOI: 10.1038/s44319-024-00186-7

Abstract

(Figure presented.) Fibroblast-specific Zeb1 knock-out in colorectal cancer models leads to a shift in myCAF and iCAF populations, promoting immune infiltration. This increases colitis-associated tumorigenesis, reduces progression and metastasis and renders tumors susceptible to immune checkpoint blockade. Zeb1 loss in cancer-associated fibroblasts (CAFs) accelerates inflammation-driven colorectal tumorigenesis. In sporadic tumors CAF-specific Zeb1-loss results in decreased progression and metastasis. Impaired myofibroblast and increased inflammation result in increased immune cell infiltration and checkpoint activation. Zeb1 deficiency in CAFs sensitizes colorectal cancers to immune checkpoint inhibition.

Authors with CRIS profile

Anne Hartebrodt Professur für Biomedical Network Science Carol-Immanuel Geppert Institute of Pathology David Blumenthal Professur für Biomedical Network Science

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Georg-Speyer-Haus DE Germany (DE) Frankfurt Cancer Institute DE Germany (DE)

How to cite

APA:

Menche, C., Schuhwerk, H., Armstark, I., Gupta, P., Fuchs, K., van Roey, R.,... Stemmler, M.P. (2024). ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer. EMBO Reports. https://doi.org/10.1038/s44319-024-00186-7

MLA:

Menche, Constantin, et al. "ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer." EMBO Reports (2024).

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