Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity
文献类型：期刊论文
| 作者 | Pei, Siyu3,7; Deng, Xiuyu7; Yang, Ruirui1; Wang, Hui3; Shi, Jian-Hong2; Wang, Xueqing7; Huang, Jia3; Tian, Yu3; Wang, Rongjing7; Zhang, Sulin1 |
| 刊名 | NATURE AGING
 |
| 出版日期 | 2024-12-01 |
| 卷号 | 4期号:12页码:1828-+ |
| DOI | 10.1038/s43587-024-00746-5 |
| 通讯作者 | Luo, Qingquan(luoqingquan@hotmail.com) ; Ni, Zhi-Yu(nizhiyu@hbu.edu.cn) ; Zheng, Mingyue(myzheng@simm.ac.cn) ; Xiao, Yichuan(ycxiao@sibs.ac.cn) |
| 英文摘要 | Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8(+) tissue resident memory T (T-RM) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8(+) T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8(+) T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by activating JAK2 deubiquitination, thereby limiting downstream STAT1-mediated T-RM reprogramming. Targeting BFAR either through Bfar knockout or treatment with our developed BFAR inhibitor, iBFAR2, rescued the antitumor activity of aged CD8(+) T cells by restoring T-RM generation in the tumor microenvironment, thus efficiently inhibiting tumor growth in aged CD8(+) T cell transfer and anti-programmed cell death protein 1 (PD-1)-resistant mouse tumor models. Together, our findings establish BFAR-induced T-RM restriction as a key mechanism causing aged CD8(+) T cell dysfunction and highlight the translational potential of iBFAR2 in restoring antitumor activity in aged individuals or patients resistant to anti-PD-1 therapy. |
| WOS关键词 | SENESCENCE ; EXHAUSTION ; RESPONSES ; PATHWAY ; STATES ; TIM-3 |
| 资助项目 | CAS Project for Young Scientists in Basic Research[YSBR-076] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39030300] ; National Natural Science Foundation of China[82425026] ; National Natural Science Foundation of China[82030041] ; National Natural Science Foundation of China[82201921] ; National Natural Science Foundation of China[82373072] ; National Natural Science Foundation of China[82273463] ; National Key R&D Program of China[2018YFA0902703] ; Shanghai Municipal Science and Technology[21140905000] ; Natural Science Foundation of Hebei Province[H2022201067] ; CAS Key Laboratory of Tissue Microenvironment and Tumor ; NovelBio Co., Ltd. |
| WOS研究方向 | Cell Biology ; Geriatrics & Gerontology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001385853600023 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315264]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Luo, Qingquan; Ni, Zhi-Yu; Zheng, Mingyue; Xiao, Yichuan |
| 作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai, Peoples R China 2.Hebei Univ, Hebei Collaborat Innovat Ctr Tumor Microecol Meta, Cent Lab, Affiliated Hosp, Baoding, Peoples R China 3.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Thorac Surg Oncol, Shanghai Lung Canc Ctr,Sch Med, Shanghai, Peoples R China 4.Hebei Univ Engn, Clin Med Coll, Handan, Peoples R China 5.Hebei Engn Univ, Affiliated Hosp, Handan, Peoples R China 6.Huazhong Univ Sci & Technol, Ctr Biomed Res, Dept Resp & Crit Care Med, Tongji Med Coll,Tongji Hosp,NHC Key Lab Resp Dis, Wuhan, Peoples R China 7.Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pei, Siyu,Deng, Xiuyu,Yang, Ruirui,et al. Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity[J]. NATURE AGING,2024,4(12):1828-+. |
| APA | Pei, Siyu.,Deng, Xiuyu.,Yang, Ruirui.,Wang, Hui.,Shi, Jian-Hong.,...&Xiao, Yichuan.(2024).Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity.NATURE AGING,4(12),1828-+. |
| MLA | Pei, Siyu,et al."Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity".NATURE AGING 4.12(2024):1828-+. |
入库方式： OAI收割
来源：上海药物研究所
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