دورية أكاديمية
IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation
| العنوان: | IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation |
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| المؤلفون: | Hui Xiong, Yu Xi, Zhiwei Yuan, Boyu Wang, Shaojie Hu, Can Fang, Yixin Cai, Xiangning Fu, Lequn Li |
| المصدر: | OncoImmunology, Vol 11, Iss 1 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | IFN-γ, STING, DNA damage, lung adenocarcinoma, T cell activation, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Stimulator of interferon genes (STING) pathway activation predicts the effectiveness of targeting the PD-1/PD-L1 axis in lung cancer. Active IFN-γ signaling is a common feature in tumors that respond to PD-1/PD-L1 blockade. The connection between IFN-γ and STING signaling in cancer cells has not been documented. We showed that IFN-γ caused DNA damage and the accumulation of cytosolic dsDNA, leading to the activation of the cGAS- and IFI16-dependent STING pathway in lung adenocarcinoma cells. IFN-γ-induced iNOS expression and nitric oxide production were responsible for DNA damage and STING activation. Additional etoposide treatment enhanced IFN-γ-induced IFN-β and CCL5 expression. Tumor-infiltrating T cells stimulated with a combination of anti-CD3 and anti-PD-1 antibodies caused STING activation and increased IFN-β and CCL5 expression in lung adenocarcinoma. These effects were abrogated by the addition of an IFN-γ neutralizing antibody. Our results suggest that the activation of tumor-infiltrating T cells could alter the tumor microenvironment via the IFN-γ-mediated activation of STING signaling in cancer cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2022.2044103 |
| URL الوصول: | https://doaj.org/article/7129a3b8a6a24344a12442ff18683b0c |
| رقم الأكسشن: | edsdoj.7129a3b8a6a24344a12442ff18683b0c |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2022.2044103 |