دورية أكاديمية
The signaling function of IDO1 incites the malignant progression of mouse B16 melanoma
| العنوان: | The signaling function of IDO1 incites the malignant progression of mouse B16 melanoma |
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| المؤلفون: | E Orecchini, ML Belladonna, MT Pallotta, C Volpi, L Zizi, E Panfili, M Gargaro, F Fallarino, S Rossini, C Suvieri, A Macchiarulo, S Bicciato, G Mondanelli, C Orabona |
| المصدر: | OncoImmunology, Vol 12, Iss 1 (2023) |
| بيانات النشر: | Taylor & Francis Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Indoleamine 2, 3-dioxygenase 1 (IDO1), immune checkpoint, immunoreceptor Tyrosine-based inhibitory motif (ITIM), IDO1 signaling function, B16 melanoma, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | ABSTRACTIndoleamine 2,3 dioxygenase 1 (IDO1), a leader tryptophan-degrading enzyme, represents a recognized immune checkpoint molecule. In neoplasia, IDO1 is often highly expressed in dendritic cells infiltrating the tumor and/or in tumor cells themselves, particularly in human melanoma. In dendritic cells, IDO1 does not merely metabolize tryptophan into kynurenine but, after phosphorylation of critical tyrosine residues in the non-catalytic small domain, it triggers a signaling pathway prolonging its immunoregulatory effects by a feed-forward mechanism. We here investigated whether the non-enzymatic function of IDO1 could also play a role in tumor cells by using B16-F10 mouse melanoma cells transfected with either the wild-type Ido1 gene (Ido1WT) or a mutated variant lacking the catalytic, but not signaling activity (Ido1H350A). As compared to the Ido1WT-transfected counterpart (B16WT), B16-F10 cells expressing Ido1H350A (B16H350A) were characterized by an in vitro accelerated growth mediated by increased Ras and Erk activities. Faster growth and malignant progression of B16H350A cells, also detectable in vivo, were found to be accompanied by a reduction in tumor-infiltrating CD8+ T cells and an increase in Foxp3+ regulatory T cells. Our data, therefore, suggest that the IDO1 signaling function can also occur in tumor cells and that alternative therapeutic approach strategies should be undertaken to effectively tackle this important immune checkpoint molecule. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X |
| العلاقة: | https://doaj.org/toc/2162-402XTest |
| DOI: | 10.1080/2162402X.2023.2170095 |
| الوصول الحر: | https://doaj.org/article/0053447a3e074a07a0905f33b03110ecTest |
| رقم الانضمام: | edsdoj.0053447a3e074a07a0905f33b03110ec |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2023.2170095 |