LAG-3及其抑制剂在肿瘤免疫治疗中应用的研究进展

Research progress on the application of LAG-3 and its inhibitors in cancer immunotherapy

淋巴细胞活化基因3(lymphocyte-activation gene 3,LAG-3)又称CD223,是一种由LAG-3基因编码的含有498个氨基酸的I型穿膜蛋白,由胞外区、穿膜区和胞内区三部分组成。LAG-3主要通过胞外区与配体结合,负向调控T淋巴细胞,避免T细胞过度激活引发自身免疫。与程序性死亡蛋白-1(programmed cell death 1,PD-1)和细胞毒性T淋巴细胞抗原4(cytotoxic T lymphocyte antigen 4,CTLA-4)一样,LAG-3是体内重要的免疫检查点,对人体免疫系统起到平衡调控作用。肿瘤细胞通过高表达LAG-3配体逃避机体免疫系统的监视。随着免疫检查点的研究逐渐深入,LAG-3成为继PD-1和CTLA-4之后新一代的免疫治疗靶点。本文主要对LAG-3的结构、功能及其抑制剂在肿瘤免疫治疗中的应用进行综述,以期为LAG-3的进一步研究提供参考。

Lymphocyte-activation gene 3(LAG-3),also known as CD223,is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene,which consists of extracellular,transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand,thus avoiding autoimmunitycaused by T cell over-activation.Like programmed cell death 1(PD-1)and cytotoxic T lymphocyte antigen 4(CTLA-4),LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand.With the development in research of immune checkpoints,LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4.This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy,in order to provide reference for the further study of LAG-3.