Статья

Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells

Yi JiangDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaShenjia GaoDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaHao SunDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaXinyi WuDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaJiahui GuDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaHan WuDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaYun LiaoSchool of Basic Medical Science, Shanghai Medical College of Fudan University, Shanghai, 200032, ChinaRonen Ben‐AmiInfectious Diseases Unit, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, IsraelChanghong MiaoDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaRong ShenDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. [email protected]Jinlong LiuInstitute of Translational Medicine, Shanghai University, Shanghai, 200444, China. [email protected]Wankun ChenDepartment of Anesthesiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201799, China. [email protected]

2024en

ABI

Аннотация

Abstract Regulatory T cells (Tregs) are a key determinant for the immunosuppressive and premetastatic niche for cancer progression after surgery resection. However, the precise mechanisms regulating Tregs function during surgical stress-facilitated cancer metastasis remain unknown. This study aims to unravel the mechanisms and explore potential strategies for preventing surgical stress-induced metastasis by targeting NEDD8. Using a surgical stress mouse model, we found that surgical stress results in the increased expression of NEDD8 in Tregs. NEDD8 depletion abrogates postoperative lung metastasis of colon cancer cells by inhibiting Treg immunosuppression and thereby partially recovering CD8 + T cell and NK cell-mediated anti-tumor immunity. Furthermore, Treg mitophagy and mitochondrial respiration exacerbated in surgically stressed mice were attenuated by NEDD8 depletion. Our observations suggest that cancer progression may result from surgery-induced enhancement of NEDD8 expression and the subsequent immunosuppressive function of Tregs. More importantly, depleting or inhibiting NEDD8 can be an efficient strategy to reduce cancer metastasis after surgery resection by regulating the function of Tregs.

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Идентификаторы

DOI: 10.1038/s41419-023-06396-6

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar