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. 2024 Aug 28:598:217098.
doi: 10.1016/j.canlet.2024.217098. Epub 2024 Jul 4.

Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2

Yang Yu  1 , Congyi Zhang  2 , Bowen Dong  3 , Zhihua Zhang  4 , Xiaoqing Li  5 , Shizhuan Huang  4 , Daowei Tang  4 , Xiaowei Jing  4 , Shan Yu  6 , Tongsen Zheng  7 , Dehai Wu  8 , Sheng Tai  9
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Free article

Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2

Yang Yu et al. Cancer Lett. .
Free article

Abstract

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.

Keywords: CD73; Hepatocellular carcinoma; Immune escape; Neutrophil extracellular traps; Notch2.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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