دورية أكاديمية
Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling
| العنوان: | Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling |
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| المؤلفون: | Zongjuan Li, Yang Zhang, Weifeng Hong, Biao Wang, Yixing Chen, Ping Yang, Jian Zhou, Jia Fan, Zhaochong Zeng, Shisuo Du |
| المصدر: | Gut Microbes, Vol 14, Iss 1 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Diseases of the digestive system. Gastroenterology |
| مصطلحات موضوعية: | Gut microbiome, hepatocellular carcinoma, radiotherapy, STING, c-di-AMP, Diseases of the digestive system. Gastroenterology, RC799-869 |
| الوصف: | Studies of the gut–liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173−/−) and cGAS-knockout (Mb21d1–/–) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS–STING–IFN-I pathway. Cyclic-di-AMP – an emerging second messenger of bacteria – may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 19490976 1949-0984 1949-0976 |
| العلاقة: | https://doaj.org/toc/1949-0976Test; https://doaj.org/toc/1949-0984Test |
| DOI: | 10.1080/19490976.2022.2119055 |
| الوصول الحر: | https://doaj.org/article/2e0a9297ed2841b3b3c809e0b1267b02Test |
| رقم الانضمام: | edsdoj.2e0a9297ed2841b3b3c809e0b1267b02 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19490976 19490984 |
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| DOI: | 10.1080/19490976.2022.2119055 |