Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
J Exp Clin Cancer Res. 2023 Sep 1;42(1):225. doi: 10.1186/s13046-023-02805-y.
Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin-proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy.
肿瘤已经进化出多种机制来逃避免疫系统，从而抑制抗肿瘤免疫反应并促进肿瘤进展。免疫疗法通过利用多种分子机制来增强针对肿瘤的免疫反应，已成为针对不同癌症类型的潜在治疗策略。在这些机制中，泛素-蛋白酶体系统（UPS）是一种特定于蛋白质降解的重要非溶酶体途径，由去泛素化酶（DUBs）调节，这些酶可抵消泛素信号。泛素特异性蛋白酶（USPs）是最大的 DUB 家族，具有最强的多样性，在调节免疫细胞功能、调节免疫反应以及参与肿瘤进展过程中的抗原加工和呈递方面发挥着关键作用。根据最近的研究，肿瘤细胞中某些 USP 家族成员的表达参与了肿瘤免疫逃逸和免疫微环境。本综述探讨了将 USPs 作为癌症免疫治疗新方法的潜力，重点介绍了最近针对 USP 抑制剂应用的基础和临床前研究。通过深入了解 USPs 在癌症免疫中的结构和功能，本综述旨在为增强免疫疗法的疗效提供新的治疗方法。
