Si-Peng WU, Xue-Yuan ZHANG, Hui-Dan CHEN, Fu-Zhi JIN, Nan JIANG, Jia-Xing ZHANG, Zhe-Long LIANG
Hepatology Forum - 2026;7(2):108-117
Background and Aim: Ubiquitin-specific protease 15 (USP15) is closely associated with the occurrence and progression of hepatocellular carcinoma (HCC). However, its role in shaping the immune landscape of HCC remains unclear. Materials and Methods: The expression levels, proportions, and spatial distributions of USP15 and specific immune cell subsets in HCC tissues were evaluated using multiplex immunohistochemistry (mIHC). Results: In the tumor parenchyma of HCC tissues, the infiltration of immune cells, particularly natural killer (NK) cells, was significantly reduced (p<0.05). Further analyses revealed that USP15 expression levels were significantly associated with clinical stage and other clinicopathological parameters (p<0.05). In particular, NK cell infiltration was significantly correlated with N stage, M stage, and overall tumor-node-metastasis (TNM) stage (p<0.05). Conclusion: USP15 contributes to the establishment of an immunosuppressive tumor microenvironment in HCC by inhibiting T cell and NK cell infiltration, facilitating programmed death-ligand 1 (PD-L1)-mediated immune evasion, and enhancing macrophage recruitment. These findings indicate that USP15 may serve as a potential therapeutic target for HCC.
