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CD103+ T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis

文献类型：期刊论文

作者Xu, Yu4; Luo, Haorui4; Wang, Jiahao4; Liu, Haifeng4; Chen, Luonan4; Ji, Hongbin4; Deng, Zimu3,4; Liu, Xiaolong1,2,4
刊名ADVANCED SCIENCE
出版日期2025-05-08
页码19
关键词AT2 cell CD103(+) T cell lung adenocarcinoma MED23 oxidative stress tumorigenesis
DOI10.1002/advs.202503557
通讯作者Deng, Zimu(dengzimu@simm.ac.cn) ; Liu, Xiaolong(liux@sibcb.ac.cn)
英文摘要The nexus between aging-associated immune deteriorations and tumorigenesis of lung cancers remains elusive. In a mouse model with Med23 depletion in T cells (Med23(-/-)), it is found a strong association between the decline of CD103(+) T cells and spontaneous alveolar epithelial type II cell (AT2 cell)-originated lung adenocarcinomas. The reduction of CD103(+) T cells in the lung results in an accumulation of AT2 cells bearing oxidative damages, which appears to be the major origin of the lung adenocarcinoma. Functional experiments reveal CD103(+) T cells can eradicate oxidative-damage-bearing AT2 cells as well as ROS-dependent, KRAS (G12D)-driven tumorigenesis. In vitro co-cultures prove CD103(+) T cells, especially CD103(+) CD8(+) T cells, exhibit a killing capacity that matches the oxidative stress level in the target cells. In aged animals, it is found the abundance of CD103(+) CD8(+) T cells in the lung declines with age, accompanied by an accumulation of oxidative-damage-bearing AT2 cells. Collectively, the study establishes the vital function of CD103(+) T cells in surveilling epithelial cells under oxidative stress to prevent malignancies, and unravels a potential immuno-dysregulation in the aged lung which contributes to tumorigenesis.
WOS关键词TUMOR-INFILTRATING LYMPHOCYTES ; CANCER-CELLS ; DNA-DAMAGE ; RNA ; SURVIVAL ; MUTATION ; ACTIVATION ; MECHANISM ; ALIGNMENT ; MARKER
资助项目National Key R&D Program of China ; National Natural Science Foundation of China[32470972] ; National Natural Science Foundation of China[31900641] ; National Natural Science Foundation of China[32170904] ; High-level Innovative Research Institute[2021B0909050003] ; Youth Innovation Promotion Association Chinese Academy of Sciences ; Sanofi-Award Fund for outstanding young talents of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences ; [2022YFA1103900] ; [2020YFA0509102] ; [2023YFA1800200] ; [2019278]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001484232500001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/317893]  
专题中国科学院上海药物研究所
通讯作者Deng, Zimu; Liu, Xiaolong
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, 319 Yueyang Rd, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci,Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Univ Chinese Acad Sci,Key Lab Multicellular Syst, 320 Yueyang Rd, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Yu,Luo, Haorui,Wang, Jiahao,et al. CD103+ T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis[J]. ADVANCED SCIENCE,2025:19.
APA Xu, Yu.,Luo, Haorui.,Wang, Jiahao.,Liu, Haifeng.,Chen, Luonan.,...&Liu, Xiaolong.(2025).CD103+ T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis.ADVANCED SCIENCE,19.
MLA Xu, Yu,et al."CD103+ T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis".ADVANCED SCIENCE (2025):19.

入库方式： OAI收割

来源：上海药物研究所

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