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TGF-β驱动的NK细胞在肝细胞癌中的可塑性

Valentina Reverberi¹, Anna Montali¹, Andrea Vecchi²

¹Department of Medicine and Surgery, University of Parma, Parma, Italy.

Frontiers in immunology

|November 21, 2025

概括

转化生长因子-β (TGF-β) 损害了自然杀手 (NK) 细胞在肝细胞癌 (HCC) 中的抗瘤功能. 准正规的TGF-β信号恢复NK细胞功能,为HCC提供新的治疗策略.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

肝细胞癌 (HCC) 是癌症死亡的主要原因,晚期的治疗选择有限.
自然杀手 (NK) 细胞对于天生的免疫是至关重要的,但在瘤免疫微环境 (TIME) 中被转化生长因子-β (TGF-β) 等因素抑制.

研究的目的:

研究TGF-β信号传导在改变NK细胞表型和功能中的作用,在HCC瘤免疫微环境中.
评估TGF-β通路激活对HCC患者NK细胞,瘤透性淋巴细胞 (TILs) 和肝脏透性淋巴细胞 (LILs) 的影响.

主要方法:

从接受切除的HCC患者中分离TIL和LIL.
对NK细胞的表型和功能分析.
针对TGF-β信号通路的功能恢复实验.

主要成果:

瘤透NK细胞 (TINKs) 显示了规范性 (SMAD依赖) 和非规范性 (TAK1/p38 MAPK) TGF-β信号的激活.
在瘤中出现了一种独特的ILC1-类NK子集 (CD103+/CD49a+),表达抑制受体,而常规NK细胞 (cNKs) 的功能受损.
阻止TGF-β受体结合和SMAD3激活成功地恢复了cNK功能.

结论:

非正规的TGF-β信号传递有助于NK细胞功能障碍和HCC的表型变化.
标准的SMAD依赖的TGF-β信号传递是恢复NK细胞功能的一种可行的治疗标.
向抑制TGF-β通路可能会增强先天的抗瘤免疫力,为HCC提供新的组合疗法选择.

关键词:

类似于ILC1的细胞在 NK 细胞中,NK 细胞是 NK 细胞.在TGF-β的基础上.功能恢复恢复功能恢复肝细胞癌是肝细胞癌.免疫功能免疫功能免疫功能

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