Álvarez Enrique, Falqui Michela, Sin Laura, McGrail Joseph Patrick, Perdiguero Beatriz, Coloma Rocío, Marcos-Villar Laura, Tárrega Céline, Esteban Mariano, Gómez Carmen Elena, Guerra Susana
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain.
Department of Preventive Medicine, Public Health and Microbiology, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Vaccines (Basel). 2024 Feb 1;12(2):153. doi: 10.3390/vaccines12020153.
The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays a crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; and (iii) exerting extracellular cytokine activity. These various roles highlight its versatility in influencing numerous cellular pathways, encompassing DNA damage response, autophagy, antiviral response, and cancer-related processes, among others. The well-established antiviral effects of ISGylation contrast with its intriguing dual role in cancer, exhibiting both suppressive and promoting effects depending on the tumour type. The multifaceted functions of ISG15 extend beyond intracellular processes to extracellular cytokine signalling, influencing immune response, chemotaxis, and anti-tumour effects. Moreover, ISG15 emerges as a promising adjuvant in vaccine development, enhancing immune responses against viral antigens and demonstrating efficacy in cancer models. As a therapeutic target in cancer treatment, ISG15 exhibits a double-edged nature, promoting or suppressing oncogenesis depending on the tumour context. This review aims to contribute to future studies exploring the role of ISG15 in immune modulation and cancer therapy, potentially paving the way for the development of novel therapeutic interventions, vaccine development, and precision medicine.
干扰素刺激基因15（ISG15）是脊椎动物特有的一种独特的类泛素（Ubl）修饰因子，在免疫系统中发挥着关键作用。ISG15主要由I型干扰素（IFN）诱导产生，通过多种机制发挥作用：（i）共价蛋白修饰（ISGylation）；（ii）非共价细胞内作用；（iii）发挥细胞外细胞因子活性。这些不同的作用突出了其在影响众多细胞途径方面的多功能性，包括DNA损伤反应、自噬、抗病毒反应和癌症相关过程等。ISGylation已确立的抗病毒作用与其在癌症中有趣的双重作用形成对比，根据肿瘤类型表现出抑制和促进作用。ISG15的多方面功能不仅扩展到细胞内过程，还涉及细胞外细胞因子信号传导，影响免疫反应、趋化性和抗肿瘤作用。此外，ISG15在疫苗开发中成为一种有前景的佐剂，增强针对病毒抗原的免疫反应，并在癌症模型中显示出疗效。作为癌症治疗的一个靶点，ISG15具有双刃剑的性质，根据肿瘤背景促进或抑制肿瘤发生。这篇综述旨在为未来探索ISG15在免疫调节和癌症治疗中作用的研究做出贡献，可能为新型治疗干预措施的开发、疫苗开发和精准医学铺平道路。
