流体结构和纤维细胞亚群对肝细胞癌的结果产生相反的影响
Yifei Cheng1, Xiaofang Chen2,3,4, Li Feng5
1Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Cell discovery
|January 27, 2025
概括
与癌症相关的纤维细胞 (CAF) 在肝细胞癌 (HCC) 中表现出空间异质性. 针对特定的CAF子集,如CAF-FAP,与免疫疗法一起,改善瘤回归,提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 癌症相关纤维细胞 (CAF) 的空间异质性对于理解瘤生物学和开发有效的癌症疗法至关重要.
- 肝细胞癌 (HCC) 层表现出复杂的细胞和分子变异,影响疾病的进展.
研究的目的:
- 为了剖析HCC中CAF的空间异质性.
- 识别不同的CAF子集及其在瘤微环境中的功能作用.
- 探索针对HCC中CAF异质性的新型治疗策略.
主要方法:
- 病理图像分析和空间蛋白质组学的整合.
- 配对单细胞RNA和表观基因组测序使用立体测序技术.
- 在体内研究使用正方形HCC模型.
主要成果:
- 在HCC中鉴定出两种独特的树叶原型,具有独特的生物功能和细胞外基质组成.
- 发现了两个纤维细胞子集,CAF-FAP和CAF-C7,在这些原型中空间丰富,与患者预后相关.
- 描述两个功能单元:一个内炎症中心 (CAF-FAP/CD8_PDCD1) 和一个边缘伤口愈合中心 (CAF-C7/Macrophage_SPP1).
- 在HCC模型中,CAF-FAP抑制和抗PD-1的联合治疗表明,与单一治疗相比,瘤回归效果优越.
结论:
- CAFs表现出上下文依赖的转录程序和细胞间交叉通话.
- 定义的树皮原型为HCC的树皮向治疗策略提供了基础.
- 针对特定的CAF子集提供了一种有希望的方法来提高HCC的免疫疗法疗效.
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