中性细胞细胞外陷-STC1正反循环促进免疫逃避和膀癌转移
Tingting Cai1,2, Tao Feng3, Wei Zhang1
1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Journal for immunotherapy of cancer
|November 28, 2025
概括
中性细胞外细胞陷 (NETs) 通过形成STC1反循环来驱动膀癌 (BLCA) 抵抗免疫疗法. 针对这个NETs-STC1轴可以克服耐药性并改善治疗结果.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 免疫检查点抑制剂 (ICI) 对膀癌 (BLCA) 有希望,但初级耐药性很常见.
- 中性粒细胞外细胞陷 (NETs) 与癌症治疗耐药性有关,但它们在BLCA中的作用尚不清楚.
研究的目的:
- 调查NETs在BLCA中的作用及其对免疫疗法耐药性的影响.
- 阐明BLCA中NETs介导抗性的分子机制.
主要方法:
- 用ICI治疗的临床队列的综合分析.
- 在体外和体内实验包括免疫光学,共同培养系统,电子显微镜和小鼠转移模型.
- 蛋白质组学和单细胞转录组学用于识别分子通路.
主要成果:
- NETs在BLCA中积累,促进转移和免疫疗法耐药性.
- NETs通过TLR2-MAPK-FosL1通路在瘤细胞中的STC1上调,抑制抗原呈现并促进NET形成.
- 分泌的STC1会损害树突细胞分化,恶化免疫抑制.
结论:
- 一个NETs-STC1反循环驱动BLCA中的免疫抵抗.
- 针对NETs-STC1轴提供了一个潜在的战略,以提高ICI的有效性和安全性.
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