TMEM199通过激活IFNGR1/2的循环,促进PD-L1表达和瘤免疫逃避
Ting Li1, Miner Xie2, Ruhua Zhang1
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
Cancer letters
|November 30, 2025
概括
跨膜蛋白199 (TMEM199) 调节干扰素 (IFN-γ) 诱导的PD-L1表达,这是癌症免疫疗法期间T细胞耗尽的关键因素. 准TMEM199可能会提高免疫检查点阻塞疗法的有效性.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 针对PD-1/PD-L1轴的免疫检查点阻塞 (ICB) 疗法在各种癌症中提供临床益处.
- 然而,持续的干扰素- (IFN-γ) 信号调节PD-L1,导致T细胞耗尽并限制ICB疗效.
- 了解IFN-γ-PD-L1信号的调节对于改善癌症免疫治疗至关重要.
研究的目的:
- 为了确定IFN-γ驱动的PD-L1转录的新型调节者.
- 阐明这些调节器影响PD-L1表达的分子机制.
- 探索增强ICB治疗的潜在治疗点.
主要方法:
- 鉴定TMEM199作为IFN-γ-PD-L1信号的调节者.
- 研究TMEM199,CCDC115和IFNGR1/2.2.之间的相互作用.
- 对蛋白质贩运到RAB11A阳性循环内分泌体的分析.
- 对TRAPP II招聘和RAB11A激活的评估.
主要成果:
- TMEM199被确定为IFN-γ诱导的PD-L1转录的新型调节剂.
- TMEM199和CCDC115促进了IFNGR1/2的贩运以回收内分泌物.
- TMEM199/CCDC115综合体招募TRAPP II并激活RAB11A,从而增强IFNGR1/2的回收.
- 这一过程导致PD-L1上调的增加.
结论:
- TMEM199在调节IFN-γ介导的PD-L1表达方面发挥着至关重要的作用.
- TMEM199/CCDC115复合体调节了IFNGR1/2的交易和信号.
- TMEM199是一个潜在的治疗目标,可以克服对ICB治疗的耐药性.
关键词:
IFNGR1/2 的时间.在PD-L1中.回收回收是回收的过程.在1991年,TEMEM1991年,TEMEM1992年,TEMEM1993年,TEMEM1993年,TEMEM1994年,TEMEM1993年,TEMEM1994年,TEMEM1993年,TEMEM1994年,TEMEM1993年,TEMEM1994年,TEMEM1993年,TEMEM1994年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEMEM1999年,TEM
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