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在人类PDAC中癌症相关纤维细胞的转录组景观

Mengyu Tao¹, Wenting Liu^2,3, Jianhua Chen^2,3

¹Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200800, P. R. China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|February 28, 2025

概括

癌症相关纤维细胞 (CAFs) 是胰腺癌的关键. 这项研究绘制了9种CAF亚型,揭示了一些与糟糕的结果有关,而另一些则表现出可塑性,提供了新的治疗点.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
免疫学免疫学免疫学

背景情况:

癌症相关纤维细胞 (CAF) 是胰腺管腺癌 (PDAC) 瘤微环境 (TME) 的关键组成部分.
了解CAF异质性和可塑性对于开发有效的癌症疗法至关重要.

研究的目的:

在人类PDAC瘤微环境 (TME) 中全面地绘制癌症相关纤维细胞 (CAF) 亚型.
研究CAFs的分化可塑性和细胞间相互作用.
确定与临床结果和潜在的治疗脆弱性相关的CAF亚型.

主要方法:

对人类PDAC瘤的综合单细胞RNA测序分析.
不同的CAF亚型的识别和表征.
分析CAF分化途径和与其他免疫细胞的相互作用.

主要成果:

确定了正常纤维细胞 (NFs) 和九种不同的CAF亚型,包括新型CDCP1+FTL+CAF,过渡CAF (tCAF),干扰素刺激基因 (ISG) +肌纤维细胞CAF (myCAF) 和增殖CAF (pCAF).
CDCP1+FTL+CAFs,pCAFs和ISG+myCAFs与不利的临床结果相关.
发现了CAF的可塑性,从nCAF过渡到iCAF和myCAF,并确定了AP-1,TGFβ和IFNγ等调节因素.
观察到CAFs和髓状细胞,特别是中性粒细胞之间的显著相互作用,由CXCR4-CXCL12信号传递介导.

结论:

这项研究提供了PDAC中CAF异质性和可塑性的详细地图.
特定的CAF亚型与预后不佳有关,并具有明显的代谢和免疫相关特征.
了解CAF的动态和相互作用为开发针对PDAC的向组合疗法提供了关键的见解.

关键词:

一个AP-1家族.在 CAF 中,CAF 是 CAF.在CDCP1中,CDCP1是指CDCP1.我们的PDAC是PDAC.异质性的异质性

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