GPRC5A+ myCAFs通过TGF-β诱导的纤维细胞激活和ANXA1-介导的M2巨细胞两极化促进ESCC的进展
Xiang Lv1, Ming Liu1, Jing Chen2
1Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China; Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China.
International immunopharmacology
|October 13, 2025
概括
与癌症相关的纤维细胞 (CAF) 促进食道状细胞癌 (ESCC) 的进展. 一个特定的GPRC5A阳性myCAF子集推动瘤生长和免疫抑制,提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 癌症相关纤维细胞 (CAF) 在食道状细胞癌 (ESCC) 中显著影响瘤微环境.
- CAFs重塑免疫系统,并通过分泌的因素促进疾病的进展.
研究的目的:
- 在ESCC中识别和描述不同的CAF子集.
- 阐明CAF特定亚种群在ESCC进展和免疫调节中的作用.
主要方法:
- 15个ESCC和11个正常食道组织的单细胞RNA测序 (scRNA-seq).
- 大量转录基因解卷用于验证基因标记物.
- 使用初级细胞模型研究CAF介导机制的功能研究.
主要成果:
- 一个由GPRC5A标记的终端分化肌纤维细胞 (myCAF_1) 子集被确定并发现在ESCC瘤中扩大.
- GPRC5A+ myCAFs激活TGF-β/SMAD2/3通路,促进正常纤维细胞转化为CAF.
- 这些CAFs分泌ANXA1,招募单细胞并将它们两极分化为免疫抑制M2瘤相关巨细胞 (TAMs).
结论:
- GPRC5A是ESCC中一种亲瘤CAF子集的特定标志物.
- 在GPRC5A/TGF-β/ANXA1轴驱动ESCC的进展和免疫逃避.
- 针对这一轴为ESCC提供了一个有前途的治疗策略.
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