通过PLAT信号调节CAF-免疫细胞相互作用,高脂肪饮食会影响乳腺癌的进展
Weihan Li1, Jiangshan He2,3, Jingjing Li4
1Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, PR China.
The Journal of pathology
|September 3, 2025
概括
通过改变瘤微环境的相互作用来促进乳腺癌. 与癌症相关的纤维细胞,特别是通过PLAT信号,影响免疫细胞,加速疾病的进展.
科学领域:
- 癌症学
- 免疫学
- 代谢过程
背景情况:
- 瘤微环境 (TME) 的相互作用,特别是与癌症相关的纤维细胞 (CAF) 和免疫细胞之间的相互作用,极大地影响了乳腺癌的进展.
- 饮食因素,如高脂肪饮食 (HFD),可以显著影响TME和癌症的发展.
研究的目的:
- 研究CAF在HFD条件下如何调节TME内的免疫细胞.
- 确定CAF中影响免疫细胞行为的关键基因及其与乳腺癌进展和患者结果的关联.
主要方法:
- 对来自乳腺癌患者的单细胞和大量RNA测序数据 (TCGA-BRCA,GEO数据集) 的分析.
- 在体内小鼠模型和体内细胞培养实验中评估CAF-免疫细胞相互作用和基因表达.
- 候选基因与患者生存,免疫细胞透和临床特征的相关性分析.
主要成果:
- 在乳腺癌患者中,HFD与CAF免疫细胞通信的改变以及肌体和免疫评分的降低有关.
- 鉴定出CAF标记基因PLAT是与免疫细胞透相关的关键因素.
- 在体内,HFD促进了与瘤相关的巨细胞透,并抑制了CD4+ T细胞激活.
- 减少了PLAT表达,促进了M2巨分化,并在体外增强了癌细胞的入侵和迁移.
结论:
- HFD通过调节CAF与免疫细胞的相互作用来重塑乳腺癌的TME,从而可能加速进展.
- 在HFD诱导的乳腺癌中,PLAT信号传递成为关键的调解者,影响免疫细胞透和巨分化.
- 针对CAF-免疫细胞交叉通话,特别是PLAT信号传递,可能为HFD相关的乳腺癌提供治疗策略.
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