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Publication : IL-1R signaling drives enteric glia-macrophage interactions in colorectal cancer.

First Author  van Baarle L Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  6079
PubMed ID  39030280 Mgi Jnum  J:352029
Mgi Id  MGI:7704628 Doi  10.1038/s41467-024-50438-2
Citation  van Baarle L, et al. (2024) IL-1R signaling drives enteric glia-macrophage interactions in colorectal cancer. Nat Commun 15(1):6079
abstractText  Enteric glia have been recently recognized as key components of the colonic tumor microenvironment indicating their potential role in colorectal cancer pathogenesis. Although enteric glia modulate immune responses in other intestinal diseases, their interaction with the colorectal cancer immune cell compartment remains unclear. Through a combination of single-cell and bulk RNA-sequencing, both in murine models and patients, here we find that enteric glia acquire an immunomodulatory phenotype by bi-directional communication with tumor-infiltrating monocytes. The latter direct a reactive enteric glial cell phenotypic and functional switch via glial IL-1R signaling. In turn, tumor glia promote monocyte differentiation towards pro-tumorigenic SPP1(+) tumor-associated macrophages by IL-6 release. Enteric glia cell abundancy correlates with worse disease outcomes in preclinical models and colorectal cancer patients. Thereby, our study reveals a neuroimmune interaction between enteric glia and tumor-associated macrophages in the colorectal tumor microenvironment, providing insights into colorectal cancer pathogenesis.
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