免疫逃逸是免疫治疗对肝细胞癌（HCC）无效的主要原因。在此，本研究阐明了中性粒细胞胞外陷阱 (NET) 介导的可促进 HCC 免疫逃逸的途径。从机制上讲，我们证明NETs通过激活Notch2介导的核因子κB（NF-κB）通路上调CD73表达，促进调节性T细胞（Treg）浸润，介导HCC的免疫逃逸。此外，我们通过流体动力学质粒转染在小鼠 HCC 模型中发现了类似的结果。脱氧核糖核酸酶I（DNase I）的治疗可以抑制NETs的作用并提高抗程序性细胞死亡蛋白1（PD-1）的治疗效果。总之，我们的结果表明，靶向 NET 是一种有前途的治疗方法，可以提高抗 PD-1 的治疗效果。版权所有 © 2024。由 Elsevier B.V. 出版。

Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.Copyright © 2024. Published by Elsevier B.V.