IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING
Endometrial carcinoma (EC) is a commonly diagnosed gynecological malignancy. Interleukin-6 (IL6) plays a critical role in modulating the progression of several types of tumors, including EC. However, the specific mechanism of IL6 in regulating EC progression has not been clearly elucidated. In this...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3815853 |
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| author | Xue Zeng Xiaosong Li Yundong Zhang Chaoxia Cao Qin Zhou |
| author_facet | Xue Zeng Xiaosong Li Yundong Zhang Chaoxia Cao Qin Zhou |
| author_sort | Xue Zeng |
| collection | DOAJ |
| description | Endometrial carcinoma (EC) is a commonly diagnosed gynecological malignancy. Interleukin-6 (IL6) plays a critical role in modulating the progression of several types of tumors, including EC. However, the specific mechanism of IL6 in regulating EC progression has not been clearly elucidated. In this study, we performed a series of functional experiments to explore the potential mechanisms involved in IL6 function in the progression of EC. Here, we found that IL6 increased reactive oxygen species (ROS) generation by enhancing the NADPH oxidase (NOX) level and induced mtDNA leakage in EC cells, which further caused the activation of the downstream cGAS-STING signaling and increased production of extracellular vesicle (EV) production from EC cells. Besides, the activation of cGAS-STING signaling enhanced the expression of type I IFN and its downstream molecule PD-L1 through the TBK1-IRF3 pathway. Importantly, a high level mtDNA and PD-L1 were present in EVs derived from IL6-induced EC cells; these vesicles were shown to be able to induce T cell apoptosis. Finally, anti-PD-L1 treatment in mice showed that blockade of PD-L1 significantly reversed tumor immune escape mediated by IL6-induced EVs. Together, we provide evidence that IL6 induced mtDNA leakage to regulate the immune escape of EC cells. Our findings may provide a novel clue for the development of therapeutic targets for EC. |
| format | Article |
| id | doaj-art-736a7e0636b34181be03370565059170 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-736a7e0636b34181be033705650591702025-02-03T01:06:37ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3815853IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STINGXue Zeng0Xiaosong Li1Yundong Zhang2Chaoxia Cao3Qin Zhou4Department of NeurologyDepartment of GynaecologyDepartment of NeurologyDepartment of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyEndometrial carcinoma (EC) is a commonly diagnosed gynecological malignancy. Interleukin-6 (IL6) plays a critical role in modulating the progression of several types of tumors, including EC. However, the specific mechanism of IL6 in regulating EC progression has not been clearly elucidated. In this study, we performed a series of functional experiments to explore the potential mechanisms involved in IL6 function in the progression of EC. Here, we found that IL6 increased reactive oxygen species (ROS) generation by enhancing the NADPH oxidase (NOX) level and induced mtDNA leakage in EC cells, which further caused the activation of the downstream cGAS-STING signaling and increased production of extracellular vesicle (EV) production from EC cells. Besides, the activation of cGAS-STING signaling enhanced the expression of type I IFN and its downstream molecule PD-L1 through the TBK1-IRF3 pathway. Importantly, a high level mtDNA and PD-L1 were present in EVs derived from IL6-induced EC cells; these vesicles were shown to be able to induce T cell apoptosis. Finally, anti-PD-L1 treatment in mice showed that blockade of PD-L1 significantly reversed tumor immune escape mediated by IL6-induced EVs. Together, we provide evidence that IL6 induced mtDNA leakage to regulate the immune escape of EC cells. Our findings may provide a novel clue for the development of therapeutic targets for EC.http://dx.doi.org/10.1155/2022/3815853 |
| spellingShingle | Xue Zeng Xiaosong Li Yundong Zhang Chaoxia Cao Qin Zhou IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING Journal of Immunology Research |
| title | IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING |
| title_full | IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING |
| title_fullStr | IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING |
| title_full_unstemmed | IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING |
| title_short | IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING |
| title_sort | il6 induces mtdna leakage to affect the immune escape of endometrial carcinoma via cgas sting |
| url | http://dx.doi.org/10.1155/2022/3815853 |
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