IL-1R signaling drives enteric glia-macrophage interactions in colorectal cancer
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...
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Veröffentlicht in: | Nature communications 2024-07, Vol.15 (1), p.6079-22, Article 6079 |
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Sprache: | eng |
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Zusammenfassung: | 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
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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.
Few studies have suggested that enteric glial cells (EGCs) promote colorectal cancer growth. Here the authors show that EGC-derived IL-6 promotes the expansion of tumorigenic SPP1
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tumor-associated macrophages, associated with worse disease outcome. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-024-50438-2 |