表皮-介质细胞转换与三阴性乳腺癌的免疫组成和细胞毒性功能的改变有关
Hanxu Lu1, Meisam Bagheri1, Fred W Kolling2
1Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
乳腺癌中的上皮介质转变 (EMT) 逐渐降低瘤免疫性,并改变免疫细胞功能. 了解跨EMT状态的这些变化是克服治疗耐药性的关键.
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:
- 表皮-介质细胞转换 (EMT) 在乳腺癌进展,转移和治疗耐药性方面至关重要.
- EMT显著影响瘤免疫微环境,影响免疫细胞透和功能.
- 中期或部分EMT状态的免疫格局是不太了解的.
研究的目的:
- 研究一系列EMT表型在乳腺癌中的免疫后果.
- 在体内描述与不同EMT状态相关的免疫细胞组成和功能.
- 阐明EMT进展如何影响瘤免疫性和免疫逃避.
主要方法:
- 从4T1小鼠乳腺瘤细胞系中建立了五个单细胞衍生的克隆群体,代表了一系列EMT表型.
- 通过单细胞RNA测序来分析这些克隆产生的瘤,以评估EMT状态和免疫透.
- 免疫细胞组成的量化变化,基因表达 (MHC,效应分子) 和沿着EMT频谱的功能途径.
主要成果:
- 来自克隆的瘤在体内保留了它们相对的EMT状态,表明随着EMT进展,瘤免疫性逐渐减少.
- EMT进展与MHC类I和II的下调相关,降低了CD8+T细胞透率,并减少了效应基因表达 (Gzmb,Ccr5,Cxcr6).
- 观察到B细胞组成的变化 (IgG1+血细胞减少,富含调节性B细胞) 和自然杀手 (NK) 细胞的功能抑制.
结论:
- EMT的进展与免疫细胞招募和功能的分级改变有关,导致免疫抑制.
- 降低MHC和效应分子的调节,以及改变免疫细胞透和功能,有助于EMT期间的免疫抵抗.
- 将EMT表型化整合到治疗策略中可能有助于克服乳腺癌中的免疫抵抗.
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