Tharuka Mohottige D Neranjan, Courelli Asimina S, Chen Yuan
Division of Surgical Sciences, Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Nat Rev Immunol. 2025 Mar 19. doi: 10.1038/s41577-025-01155-4.
Post-translational protein modifications by the small ubiquitin-like modifier (SUMO) family have been shown to regulate immune cells in the context of infection, autoimmunity and, more recently, cancer. Recent clinical trials investigating sumoylation inhibition as a therapeutic approach for cancer have established that sumoylation has important immune modulatory effects. Sumoylation suppresses transcription factors in innate immune cells and in cytotoxic T cells through the direct modification of these factors, which leads to the recruitment of transcriptional repressor complexes containing histone deacetylases. By contrast, in regulatory T cells and T helper 17 cells, sumoylation of transcription factors can enhance transcriptional activity by recruiting transcriptional coactivators. Sumoylation is also involved in the repression of IFNB1 and endogenous retroviruses and is therefore important for regulating interferon expression. A central theme from literature is that the sumoylation of a group of proteins, instead of a single target, collectively contributes to the regulation of various immune processes. In this Review, we consider how these studies provide scientific basis for future exploration of SUMO-mediated immune modulation for the treatment of cancers and autoimmune disorders.
小泛素样修饰物（SUMO）家族对蛋白质的翻译后修饰已被证明在感染、自身免疫以及最近发现的癌症背景下对免疫细胞具有调节作用。最近关于抑制SUMO化作为癌症治疗方法的临床试验表明，SUMO化具有重要的免疫调节作用。SUMO化通过直接修饰先天免疫细胞和细胞毒性T细胞中的转录因子来抑制这些因子，这会导致募集含有组蛋白脱乙酰酶的转录抑制复合物。相比之下，在调节性T细胞和辅助性T细胞17中，转录因子的SUMO化可通过募集转录共激活因子来增强转录活性。SUMO化还参与对IFNB1和内源性逆转录病毒的抑制，因此对调节干扰素表达很重要。文献中的一个核心观点是，一组蛋白质而非单个靶点的SUMO化共同有助于调节各种免疫过程。在本综述中，我们探讨这些研究如何为未来探索SUMO介导的免疫调节以治疗癌症和自身免疫性疾病提供科学依据。
