癌症研究
抑制因子
乳腺癌
三阴性乳腺癌
转录因子
生物
锌指
免疫系统
雌激素受体
体内
抄写(语言学)
免疫疗法
杂合子丢失
免疫学
癌症
基因
遗传学
语言学
哲学
等位基因
作者
Yuncheng Liu,Peng Yuan,Yong Du,Chunyu Yu,Zebo Peng,Ling Qin,Yihan Ma,Xue-Ru Wu,Yuan Peng,Xiao Cheng,Xueguan Lu,Huanbao Fa,Yuqing Wu,Luyang Sun,Jianying Liu,Zhihua Liu,Yongfeng Shang,Shu Wang,Jenn‐Tai Liang
出处
期刊:Cell Reports
[Elsevier]
日期:2023-11-01
卷期号:42 (11): 113343-113343
被引量:1
标识
DOI:10.1016/j.celrep.2023.113343
摘要
The intrinsic regulation of programmed death ligand-1 (PD-L1) expression remains unclear. Here, we report that zinc-finger protein 652 (ZNF652) is a potent transcription repressor of PD-L1. ZNF652 frequently experiences loss of heterozygosity (LOH) in various cancers. Higher LOH rate and lack of estrogen-inducible transcription lead to suppressed expression of ZNF652 in triple-negative breast cancer (TNBC). Mechanistically, ZNF652 is physically associated with the NuRD transcription co-repressor complex to repress a cohort of genes, including PD-L1. Overexpression of ZNF652 inhibits PD-L1 transcription, whereas depletion of ZNF652 upregulates PD-L1. Loss of ZNF652 in TNBC unleashes PD-L1-mediated immune evasion both in vitro and in vivo. Significantly, ZNF652 expression is progressively lost during breast cancer progression, and a low ZNF652 level is correlated with elevated PD-L1 expression, less infiltrated CD8+ T cells, and poor prognosis in TNBC. Our study provides insights into PD-L1 regulation and supports the pursuit of ZNF652 as a potential biomarker and drug target for breast cancer immunotherapy.
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