泛素化与去泛素化修饰在肿瘤免疫调控中的研究进展  

Research progress of ubiquitination and deubiquitination in tumor immune regulation

作　　者：张雪 石文贵 焦作义[1] ZHANG Xue;SHI Wengui;JIAO Zuoyi(Department of General Surgery,Lanzhou University Second Hospital,Lanzhou 730030,China;Cuiying Biomedical Research Center,Lanzhou University Second Hospital,Lanzhou 730030,China)

机构地区：[1]兰州大学第二医院普外科,兰州730030 [2]兰州大学第二医院萃英生物医学研究中心,兰州730030

出　　处：《中国免疫学杂志》2024年第11期2427-2433,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(32170729);甘肃省自然科学基金青年项目(21JR7RA418)。

摘　　要：泛素化是一种重要的蛋白质翻译后修饰方式,在癌症、免疫疾病等病理性过程中发挥重要调控作用。泛素化及去泛素化不仅涉及免疫细胞的活化、增殖、分化等过程,而且能调节免疫检查点,改变肿瘤患者对免疫治疗的反应率。基于此,靶向泛素化及去泛素化过程能改善抑制性肿瘤微环境,增加免疫细胞的活性和浸润数量并下调免疫检查点,进一步与免疫检查点抑制剂、化疗药物联用能显著增强抗肿瘤效果。因此,本综述重点介绍了泛素化及去泛素化酶在肿瘤浸润性免疫细胞和免疫检查点中的作用,并总结其小分子抑制剂在肿瘤治疗中的最新发现和应用,为通过靶向泛素化及去泛素化改善免疫微环境,提高肿瘤对免疫治疗的反应性提供了新思路。Ubiquitination is an important post-translational modification of proteins,which plays an important regulatory role in pathological processes such as cancer and immune diseases.Ubiquitination and deubiquitination are not only involved in the process of activation,proliferation and differentiation of immune cells,but also can regulate immune checkpoints and change the response rate of tumor to immunotherapy.Based on this,targeting the process of ubiquitination and deubiquitination can improve the inhibitory tumor microenvironment,increase the activity and infiltration number of immune cells,and downregulate immune checkpoints,which can enhance the anti-tumor effect when further combined with immune checkpoint inhibitors and chemotherapy drugs.Therefore,this review focuses on the roles of ubiquitination and deubiquitination enzymes in tumor-infiltrating immune cells and immune check-points,and summarizes the latest discoveries and applications of their small molecule inhibitors in tumor therapy.It provides a new idea to target the immune microenvironment by ubiquitination and deubiquitination,and improve the responsiveness of tumors to immunotherapy.

关 键 词：泛素化 去泛素化 肿瘤免疫 免疫检查点 

分 类 号：R392.1[医药卫生—免疫学]