Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines
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Le résumé fourni par la source
BACKGROUND: Cancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host's immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration. METHODS: We correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells. RESULTS: Increased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients' gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK. CONCLUSIONS: The expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines
- Date Crossref
- 12/10/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Nevada Department of Physiology and Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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Victoria University Institute for Health and Sport pays non établi dans la noticeUniversité ou école supérieure
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University of Warmia and Mazury in Olsztyn pays non établi dans la noticeUniversité ou école supérieure
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Gdańsk Medical University pays non établi dans la noticeUniversité ou école supérieure
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The University of Melbourne Department of Medicine Western Health pays non établi dans la noticeUniversité ou école supérieure
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Western Health pays non établi dans la noticeÉtablissement de santé
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Australian Institute for Musculoskeletal Science pays non établi dans la noticeStructure de recherche
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Medical University of Gdansk Department of Histology pays non établi dans la noticeUniversité ou école supérieure
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Australian Institute of Musculoskeletal Sciences Immunology Program pays non établi dans la noticeStructure de recherche
Department of Physiology and Cell Biology — University of Nevada, Institute for Health and Sport — Victoria University et University of Warmia and Mazury in Olsztyn, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.