脂解
脂肪甘油三酯脂肪酶
脂肪组织
脂毒性
串扰
细胞生物学
FGF21型
脂滴包被蛋白
自分泌信号
化学
脂滴
内分泌学
内科学
肿瘤微环境
细胞
脂肪因子
生物
脂质代谢
线粒体
3T3-L1
胰岛素抵抗
脂质信号
癌细胞
平衡
脂肪细胞
β氧化
葡萄糖稳态
效应器
安格普特4
分泌物
能量稳态
作者
Sumiya Dalangood,Cegui Hu,Chenwei Yuan,Xiang Li,Wen Qiao,Hanjun Li,Rongyu Zhang,Luying Li,Li Peng,Xiang Yu,Wenjin Yin,Jinsong Lu,Jun Gui
出处
期刊:Cell Reports
[Cell Press]
日期:2025-11-01
卷期号:44 (11): 116526-116526
被引量:2
标识
DOI:10.1016/j.celrep.2025.116526
摘要
Cancer-associated adipocytes (CAAs) reprogram the metabolic status of the tumor microenvironment (TME). The metabolic crosstalk between CAAs and CD8+T cells in the TME remains unclear. Here, we report that CAAs undergo lipolysis, releasing free fatty acids that promote lipid peroxidation and disturb mitochondrial homeostasis in CD8+T cells, leading to their functional exhaustion. Importantly, we uncover that fibroblast growth factor 21 (FGF21) drives CAA lipolysis in an autocrine manner by upregulating adipose triglyceride lipase (ATGL) via FGFR1/KLB-p38 signaling. FGF21 deletion in adipose tissue or ATGL inhibition impedes CAA lipolysis, mitigates lipid peroxidation, normalizes mitochondrial dynamics of CD8+T cells, and restores their effector function, consequently blunting tumor growth. Moreover, FGF21 deficiency or ATGL inhibition enhances the anti-tumor activity of CD8+T cells in response to anti-PD-1 treatment, yielding greater therapeutic efficacy. Our findings highlight the pivotal role of CAA lipolysis in CD8+T cell dysfunction within the TME, suggesting that targeting CAA lipolysis represents a valuable avenue for improving cancer immunotherapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI