TFEB
癌症研究
肿瘤微环境
下调和上调
细胞毒性T细胞
生物
免疫系统
肺癌
免疫学
医学
内科学
自噬
细胞凋亡
生物化学
基因
体外
作者
Zhen Cai,Lijie Zhou,Songyang Li,Junwei Zhao,Xianchun Meng,Liwei Ma,Yongfeng Wang,Cai Li,Zheng Lu,Liang Ming
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-12-01
卷期号:550: 215918-215918
被引量:4
标识
DOI:10.1016/j.canlet.2022.215918
摘要
Although obesity contributes to tumor incidence and progression in various cancers, whether obesity impacts the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) remains largely under-explored. We generated NSCLC xenograft model in diet-induced obese mice and identified that TFEB is critical to accelerate obesity-related NSCLC progression with mimic intrinsic functions on tumor biology. Mechanically, TFEB binds directly to Siglec-15 promoter to upregulate Siglec-15 expression and binds to Hk2 and Ldha promoters to enhance glycolytic flux in NSCLC cells, which restrain the expansion and cytotoxic function of CD8+ T cells while maintain suppressive Treg cells in TME, jointly promoting immune evasion of NSCLC cells in obesity. Blocking tumor TFEB improves the therapeutic efficiency of anti-PD-1 in obese mice. Altogether, our data identify essential roles of TFEB in remodeling immunosuppressive TME and promoting NSCLC development in obesity, providing scientific rational for TFEB as a potential biomarker to predict immune checkpoint blockade efficiency in obese NSCLC patients.
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