Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112 Halle, Germany.
Institute for Translational Immunology, Brandenburg Medical School Theodor Fontane, Hochstr. 29, 14770 Brandenburg an der Havel, Germany.
Int J Mol Sci. 2023 Apr 4;24(7):6736. doi: 10.3390/ijms24076736.
Interferons (IFNs), divided into type I, type II, and type III IFNs represent proteins that are secreted from cells in response to various stimuli and provide important information for understanding the evolution, structure, and function of the immune system, as well as the signaling pathways of other cytokines and their receptors. They exert comparable, but also distinct physiologic and pathophysiologic activities accompanied by pleiotropic effects, such as the modulation of host responses against bacterial and viral infections, tumor surveillance, innate and adaptive immune responses. IFNs were the first cytokines used for the treatment of tumor patients including hairy leukemia, renal cell carcinoma, and melanoma. However, tumor cells often develop a transient or permanent resistance to IFNs, which has been linked to the escape of tumor cells and unresponsiveness to immunotherapies. In addition, loss-of-function mutations in IFN signaling components have been associated with susceptibility to infectious diseases, such as COVID-19 and mycobacterial infections. In this review, we summarize general features of the three IFN families and their function, the expression and activity of the different IFN signal transduction pathways, and their role in tumor immune evasion and pathogen clearance, with links to alterations in the major histocompatibility complex (MHC) class I and II antigen processing machinery (APM). In addition, we discuss insights regarding the clinical applications of IFNs alone or in combination with other therapeutic options including immunotherapies as well as strategies reversing the deficient IFN signaling. Therefore, this review provides an overview on the function and clinical relevance of the different IFN family members, with a specific focus on the MHC pathways in cancers and infections and their contribution to immune escape of tumors.
干扰素 (IFNs) 分为 I 型、II 型和 III 型，是细胞受到各种刺激后分泌的蛋白质，为了解免疫系统的进化、结构和功能以及其他细胞因子及其受体的信号通路提供了重要信息。它们发挥着相似但又不同的生理和病理生理作用，并伴有多效性效应，如调节宿主对细菌和病毒感染的反应、肿瘤监测、先天和适应性免疫反应。IFNs 是最早用于治疗肿瘤患者的细胞因子之一，包括毛细胞白血病、肾细胞癌和黑色素瘤。然而，肿瘤细胞常常对 IFNs 产生短暂或永久的耐药性，这与肿瘤细胞的逃逸和对免疫疗法的无反应有关。此外，IFN 信号转导途径的不同成分的功能丧失突变与易感性传染病有关，如 COVID-19 和分枝杆菌感染。在这篇综述中，我们总结了三种 IFN 家族的一般特征及其功能、不同 IFN 信号转导途径的表达和活性，以及它们在肿瘤免疫逃逸和病原体清除中的作用，以及与主要组织相容性复合体 (MHC) I 类和 II 类抗原加工机制 (APM) 的改变有关。此外，我们还讨论了单独使用 IFN 或与其他治疗方案（包括免疫疗法）联合使用的临床应用的见解，以及逆转 IFN 信号转导缺陷的策略。因此，本综述提供了不同 IFN 家族成员的功能和临床相关性的概述，特别关注癌症和感染中的 MHC 途径及其对肿瘤免疫逃逸的贡献。
