Loss of Parp7 increases type I interferon signalling and reduces pancreatic tumour growth by enhancing immune cell infiltration
Rattachement africain : ca, no, it, ee, lv, lt. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and despite low incidence rates, it remains the sixth leading cause of cancer related deaths worldwide. Immunotherapy, which aims to enhance the immune system's ability to recognize and eliminate cancer cells, has emerged as a promising approach in the battle against PDAC. PARP7, a mono-ADP-ribosyltransferase, is a negative regulator of the type I interferon (IFN-I) pathway and has been reported to reduce anti-tumour immunity. Methods: We used murine pancreatic cancer cells, CR705, CRISPR/Cas9, in vivo tumour models and spectral flow cytometry to determine the role of PARP7 in pancreatic tumour growth. Results: Loss of Parp7 elevated the levels of interferon stimulated gene factor 3 (ISGF3) and its downstream target genes, even in the absence of STING. Cancer cells knocked out for Parp7 (CR705Parp7KO) produced smaller tumours than control cells (CR705Cas9) when injected into immunocompetent mice. Transcriptomic analyses revealed that CR705Parp7KO tumours had increased expression of genes involved in immunoregulatory interactions and interferon signalling pathways. Characterization of tumour infiltrating leukocyte (TIL) populations showed that CR705Parp7KO tumours had higher proportions of natural killer cells, CD8+ T cells and a lower proportion of anti-inflammatory macrophages (M2). The overall TIL profile of CR705Parp7KO tumours was suggestive of a less suppressive microenvironment. Conclusions: Our data show that loss of Parp7 reduces PDAC tumour growth by increasing the infiltration of immune cells and enhancing anti-tumour immunity. These findings provide support to pursue PARP7 as a therapeutic target for cancer treatment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Loss of Parp7 increases type I interferon signalling and reduces pancreatic tumour growth by enhancing immune cell infiltration
- Date Crossref
- 10/01/2025
- Éditeur
- Frontiers Media SA
- 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.
Où se fait cette recherche
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University of Toronto Department of Pharmacology and Toxicology pays non établi dans la noticeUniversité ou école supérieure
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University of Oslo pays non établi dans la noticeUniversité ou école supérieure
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University of Turin Department of Molecular Biotechnology and Health Sciences pays non établi dans la noticeUniversité ou école supérieure
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University of Tartu Institute of Molecular and Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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Latvijas Organiskās Sintēzes Institūts pays non établi dans la noticeStructure de recherche
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Lithuanian University of Health Sciences pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine Department of Nutrition pays non établi dans la noticeUniversité ou école supérieure
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Latvian Institute of Organic Synthesis pays non établi dans la noticeStructure de recherche
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Lithuanian University of Health of Sciences Surgical Gastroenterology Laboratory pays non établi dans la noticeUniversité ou école supérieure
Department of Pharmacology and Toxicology — University of Toronto, University of Oslo et Department of Molecular Biotechnology and Health Sciences — University of Turin, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.