Department of Immunology, Medical College of Qingdao University, Qingdao, Shandong 266071, PR China.
Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao, Shandong 266071, PR China.
Int Immunopharmacol. 2023 Oct;123:110757. doi: 10.1016/j.intimp.2023.110757. Epub 2023 Aug 12.
Interleukin 17A (IL-17A) is a major member of the IL-17 cytokine family and is produced mainly by T helper 17 (Th17) cells. Other cells such as CD8 T cells, γδ T cells, natural killer T cells and innate lymphoid-like cells can also produce IL-17A. In healthy individuals, IL-17A has a host-protective capacity, but excessive elevation of IL-17A is associated with the development of autoimmune diseases and cancer. Monoclonal antibodies (mAbs) targeting IL-17A (e.g., ixekizumab and secukinumab) or IL-17A receptor (IL-17RA) (e.g., brodalumab) would be investigated as potential treatments for these diseases. Currently, the application of IL-17A-targeted drugs in autoimmune diseases will provide new ideas for the treatment of tumors, and its combined application with immune checkpoint inhibitors has become a research hotspot. This article reviews the mechanism of action of IL-17A and the application of anti-IL-17A antibodies, focusing on the research progress on the mechanism of action and therapeutic blockade of IL-17A in various tumors such as colorectal cancer (CRC), lung cancer, gastric cancer and breast cancer. Moreover, we also include the results of therapeutic blockade in the field of cancer as well as recent advances in the regulation of IL-17A signaling.
白细胞介素 17A（IL-17A）是白细胞介素 17 细胞因子家族的主要成员，主要由辅助性 T 细胞 17（Th17）细胞产生。其他细胞，如 CD8 T 细胞、γδ T 细胞、自然杀伤 T 细胞和先天淋巴样细胞也可以产生 IL-17A。在健康个体中，IL-17A 具有宿主保护能力，但 IL-17A 的过度升高与自身免疫性疾病和癌症的发展有关。针对 IL-17A（例如依奇珠单抗和司库奇尤单抗）或 IL-17A 受体（IL-17RA）（例如布罗达单抗）的单克隆抗体（mAbs）将被研究作为这些疾病的潜在治疗方法。目前，IL-17A 靶向药物在自身免疫性疾病中的应用为肿瘤治疗提供了新的思路，其与免疫检查点抑制剂的联合应用已成为研究热点。本文综述了 IL-17A 的作用机制及抗 IL-17A 抗体的应用，重点介绍了 IL-17A 在结直肠癌（CRC）、肺癌、胃癌和乳腺癌等多种肿瘤中的作用机制和治疗阻断的研究进展。此外，我们还包括了癌症领域治疗阻断的结果以及 IL-17A 信号通路调节的最新进展。
