WDR4通过选择性翻译和膜胆固醇外流驱动与瘤相关的巨细胞重编程和瘤进展
Jie Liu1,2, Chengming Qu1,3, Yingyi Liu1
1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, People's Republic of China.
Nature cell biology
|November 29, 2025
概括
WDR4蛋白质通过维持前瘤巨细胞极化,促进肝细胞癌 (HCC) 的进展. 在瘤相关巨细胞 (TAMs) 中抑制WDR4可增强抗瘤免疫力,并提高免疫疗法的疗效.
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:
- 与瘤相关的巨细胞 (TAMs) 对于调节肝细胞癌 (HCC) 免疫微环境至关重要.
- 作为N7-甲基瓜诺辛 (m7G) 甲基转移酶复合体中的辅因子,WDR4在癌症中没有明确的作用.
研究的目的:
- 调查WDR4在与HCC相关的TAM中的作用.
- 探索WDR4作为HCC免疫治疗的潜在治疗点.
主要方法:
- 在HCC TAM中分析WDR4表达的分析.
- 功能性研究涉及巨细胞中WDR4敲击.
- 关于WDR4与eIF4E2和ABCA1翻译的相互作用的机制研究.
- 使用CpG-小干扰RNA传递用于WDR4沉默的体内研究.
主要成果:
- 在HCC TAM中,WDR4被上调,并与预后不佳有关.
- 巨细胞中的WDR4损失将TAM重编程为抗瘤表型,抑制HCC.
- 细胞质WDR4与eIF4E2相互作用,增强ABCA1翻译并促进瘤前TAM两极化.
- 在TAM中准WDR4沉默可以增强抗瘤免疫力,并改善抗PD-1治疗反应.
结论:
- 在HCC中,WDR4是TAM极化的一个关键调节器.
- 在TAM中准WDR4代表了增强HCC免疫疗法的有希望的策略.
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