癌症相关的纤维细胞通过WISP-1-Integrin α5β3-STAT1信号在肺癌中抑制免疫抑制巨细胞
Kyungwon Yang1,2, Kiyoon Kim2, Hee Ja Kim1
1Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
International journal of biological sciences
|January 12, 2026
概括
与癌症相关的纤维细胞释放Wnt诱导的信号蛋白1 (WISP-1),该蛋白重新编程与瘤相关的巨细胞 (TAMs) 从M2变为M1表型,增强肺癌的抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 瘤微环境 (TME) 免疫细胞动态影响癌症的进展.
- 与癌症相关的纤维细胞 (CAF) 和与瘤相关的巨细胞 (TAM) 关键调节TME免疫力.
研究的目的:
- 调查CAFs在TME内调节TAM表型中的作用.
- 确定CAFs影响TAM极化和抗瘤免疫力的分子机制.
主要方法:
- 共同培养系统使用肺CAF和M2类巨细胞与亡性癌细胞.
- 有条件介质 (CM) 转移实验.
- Wnt诱导信号蛋白1 (WISP-1) 敲除和重组蛋白质的管理.
- 综合素α5β3和STAT1信号通路分析.
- 在活体研究中,在肺癌模型中进行了内CM注射.
- 免疫细胞表型和激活标记物的流细胞计和免疫组织化学.
主要成果:
- 由CAF衍生的CM诱导了M2 TAM细胞亡和M1重编程,由WISP-1介导.
- 通过整合蛋白α5β3-STAT1轴传递WISP-1信号对于M2 TAM亡和M1重编程至关重要.
- 在体内,CM治疗降低了M2TAMs,促进了M1两极分化,增加了CD8+T细胞透,降低了调控性T细胞.
- 消耗WISP-1或抑制STAT1会取消这些抗瘤作用.
结论:
- WISP-1-整合素α5β3-STAT1轴是CAF诱导的TAM重编程的一个关键媒介.
- 针对这一轴具有增强抗瘤免疫力和抑制肺癌生长的治疗潜力.
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