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DysUFMylation重新编程免疫抑制性中性粒细胞,以加强肝细胞癌中抗PD-1疗法

Xukang Gao¹, Min Xu², Zeping Han¹

¹Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China; Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China; Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, 200032, P. R. China.

|March 4, 2026

概括

在肝细胞癌 (HCC) 中低UFL1表达通过减少免疫抑制性中性粒细胞和增强CD8+T细胞来提高抗瘤免疫力. 这一发现为改善HCC患者免疫治疗反应提供了一个新的目标.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

免疫检查点阻塞在肝细胞癌 (HCC) 中具有有限的益处.
了解耐药机制和预测生物标志物对于改善HCC免疫疗法至关重要.
在HCC免疫微环境中UFL1-介导的UFMylation的作用尚未被探索.

研究的目的:

研究UFL1-介导的UFMylation在HCC免疫微环境中的作用.
为了确定 HCC. 免疫疗法耐药性的基础机制.
发现HCC免疫治疗的预测生物标志物和治疗点.

主要方法:

在HCC模型和患者样本中分析UFL1表达.
研究UFL1对免疫细胞透和功能 (CD8+T细胞,中性粒细胞) 的影响.
涉及PRMT5,NF-κB p65和CXCL8信号的机制研究.
对UFL1抑制和CXCL8阻断与抗PD-1疗法结合的评估.

主要成果:

低UFL1表达与增强的CD8+T细胞透和细胞毒性相关.
由于UFL1缺乏,可以通过UFL1-PRMT5-NF-κB p65-CXCL8轴减少与瘤相关的中性粒细胞透和N2极化.
低UFL1表达与抗PD-1疗法协同,以改善HCC模型中的存活率.
从临床上看,免疫疗法响应者显示UFL1,PRMT5,CXCL8和中性粒细胞透率降低,CD8+T细胞活性升高.

结论:

通过UFL1介导的UFMylation对HCC免疫微环境进行了关键调节.
在UFL1-PRMT5-NF-κB p65-CXCL8轴驱动中性粒细胞介导的免疫抑制在HCC.
CXCL8 作为预测生物标志物和治疗点,用于增强HCC免疫疗法.

关键词:

在DysUFMylation中进行了化.肝细胞癌是肝细胞癌.瘤的免疫微环境与瘤相关的中性粒细胞抗PD-1疗法的治疗.

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