来自纤维细胞的PI16通过诱导Tregs分化来增强瘤免疫抑制的微环境
Daqin Suo1,2, Lily Liang1,2, Zengfei Xia1,2
1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
Cellular oncology (Dordrecht, Netherlands)
|July 22, 2025
概括
纤维细胞衍生PI16 (酶抑制剂16) 在食道状细胞癌 (ESCC) 中促进调节性T细胞 (Treg) 分化. 向PI16+纤维细胞可以克服瘤免疫抑制并改善患者的生存率.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 食道状细胞癌 (ESCC) 是积极的,预后不佳.
- 瘤微环境 (TME) 极大地影响癌症的进展和治疗反应.
- 在TME内的纤维细胞,特别是淋巴结中的纤维细胞,已通过酶抑制剂16 (PI16) 对ESCC细胞产生药物耐药性.
研究的目的:
- 研究纤维细胞衍生PI16在ESCC瘤微环境中的作用.
- 阐明PI16影响TME内的免疫细胞的机制.
- 评估PI16表达在ESCC患者的预后意义.
主要方法:
- 对ESCC.的公共单细胞RNA测序数据 (GSE203115) 的分析.
- 细胞共同培养试验用于研究调节性T细胞 (Treg) 与原始CD4+T细胞的分化.
- 免疫沉,质谱,体外/体内测定和多重光免疫组织化学 (mfIHC) 测定PI16的功能和机制,涉及DOCK2.
主要成果:
- 在ESCC瘤中的纤维细胞被分为PI16表达 (PI16+) 和非表达 (PI16-) 种群.
- 发现PI16通过DOCK2依赖的途径诱导Treg与原始CD4+T细胞的分化.
- 在体内抑制DOCK2抑制PI16诱导的Treg分化并增强效应T细胞 (Teff) 透.
- 瘤侧膜中PI16水平升高与ESCC患者的长期生存结果较差相关.
结论:
- 产生PI16的纤维细胞通过DOCK2相互作用促进Treg分化,有助于ESCC中的免疫抑制.
- 高层PI16表达是ESCC患者的负预后标志物.
- 准PI16+纤维细胞是扭转ESCC瘤免疫抑制的潜在治疗策略.
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