与细胞死亡相关的预后基因调节了三阴性乳腺癌中免疫微环境的失调
Xiaowen Ma1, Hui Shan2, Zhao Chen3
1Pharmacy Department, 960th Hospital of the Joint Logistic Support Force, Jinan, Shandong, China.
Frontiers in immunology
|March 27, 2025
概括
编程细胞死亡 (PCD) 通过改变瘤微环境 (TME) 来影响三阴性乳腺癌 (TNBC) 的进展和治疗耐药性. 阳性CEBPB癌症相关纤维细胞 (CAF) 是TNBC异质性和免疫逃避的关键驱动因素,影响预后.
科学领域:
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 编程细胞死亡 (PCD) 在三阴性乳腺癌 (TNBC) 的进展和治疗耐药性中起着复杂的作用.
- 在TNBC中PCD介导的瘤微环境 (TME) 失调的机制尚不清楚.
研究的目的:
- 阐明PCD在调节TNBC TME中的作用.
- 确定关键细胞群和参与PCD介导的TNBC病原和免疫抵抗的信号通路.
主要方法:
- 在9个TNBC样本中进行单细胞RNA测序 (scRNA-seq).
- 非负矩阵因子化 (NMF) 用于PCD基因评估.
- SCENIC,Monocle,CellChat和scMetabolism用于假名时间,细胞间通信,TF活动和免疫透分析.
- 使用GSEA,Kaplan-Meier和Cox回归的预测模型构建和耐药性分析.
- 在临床样本和TNBC小鼠模型中的验证.
主要成果:
- 在TNBC TME中,PCD显著改变纤维细胞,巨细胞,T细胞和B细胞群.
- 受到PCD调控的CEPBPB阳性癌症相关纤维细胞 (CAF) 是TNBC免疫异质性和不良预后的关键决定因素.
- 中基因 (MDK) - 核素 (NCL) 信号轴介导CEPB + CAF和其他免疫细胞之间的相互作用.
- CEBPB + CAFs预测免疫疗法反应不佳.
结论:
- 这项研究建立了一个分子框架,以了解TNBC中PCD介导的TME失调.
- 确定CEBPB+ CAF和MDK-NCL轴作为改善TNBC免疫疗法和患者结果的潜在治疗点.
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