泛素特异性肽酶 24 (USP24) 是去泛素酶家族的成员，在肿瘤调节中发挥着重要作用。然而，USP24在肝细胞癌（HCC）中的作用尚不清楚。本研究的目的是探讨USP24在HCC中的作用，以寻找HCC新的治疗靶点。在这项研究中，我们发现 USP24 在 HCC 组织中异常上调，并预测预后不良。 USP24 在体外和体内显着促进 HCC 增殖和进展。从机制上讲，USP24与肿瘤坏死因子受体相关因子2（TRAF2）结合并抑制其降解，从而促进TRAF2的积累。 TRAF2 上调激活蛋白激酶 B/核因子 kappa-B (AKT/NF-κB) 信号通路并促进 HCC 细胞存活。此外，USP24与HCC中程序性细胞死亡配体1（PD-L1）的表达呈正相关，凸显了USP24激活在肿瘤免疫逃避中的临床意义。 USP24的缺失增强了CD8 T细胞的肿瘤杀伤能力。删除USP24联合抗PD-1抗体显着增强HCC免疫治疗的疗效。总而言之，USP24 可以作为抑制肿瘤生长和提高 HCC 免疫治疗疗效的有前景的靶点。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Ubiquitin-specific peptidase 24 (USP24), a member of the deubiquitinase family, plays an important role in tumor regulation. However, the role of USP24 in Hepatocellular carcinoma（HCC）is unknown. The aim of our study was to explore the role of USP24 in HCC to seek new therapeutic targets for HCC. In this study, we found that USP24 was aberrantly upregulated in HCC tissues and predicted poor prognosis. USP24 markedly promoted HCC proliferation and progression in vitro and in vivo. Mechanistically, USP24 binds to tumor necrosis factor receptor-associated factor 2(TRAF2) and inhibits its degradation, thereby promoting the accumulation of TRAF2. Upregulation of TRAF2 activated protein kinase B/nuclear factor kappa-B (AKT/ NF-κB) signaling pathway and promoted HCC cell survival. In addition, USP24 positively correlated with programmed cell death ligand 1(PD-L1) expression in HCC, highlighting the clinical significance of USP24 activation in tumor immune evasion. Deletion of USP24 enhanced the tumor-killing ability of CD8+ T cells. Deletion of USP24 combined with anti-PD-1 antibody significantly enhanced the efficacy of HCC immunotherapy. Taken together, USP24 can be employed as a promising target to restrain tumor growth and increase the efficacy of HCC immunotherapy.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.