中国肿瘤生物治疗杂志2025，Vol.32Issue(12)：1211-1220,10.DOI:10.3872/j.issn.1007-385x.2025.12.001
免疫检查点LAG-3的功能机制与临床应用
Molecular mechanisms and clinical applications of the immune checkpoint LAG-3
摘要
Abstract
Lymphocyte activation gene-3(LAG-3,CD223)plays a pivotal role in regulating T-cell function and maintaining immune homeostasis and is widely recognized as the most promising co-inhibitory immune checkpoint following programmed death-1(PD-1)and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4).LAG-3 is highly expressed on activated T cells and exhausted T cells(TEX)within the tumor microenvironment,where its inhibitory activity constitutes a critical mechanism underlying tumor immune evasion.In contrast to PD-1 and CTLA-4,LAG-3 exhibits distinct regulatory features in modulating T-cell receptor(TCR)signaling strength and restricting T-cell proliferation and effector cytokine production.Consequently,LAG-3 is broadly regarded as one of the most clinically promising immune checkpoint targets beyond PD-1 and CTLA-4.In recent years,advances in the understanding of LAG-3 molecular structure,extracellular ligand interactions(e.g.,major histocompatibility complex class Ⅱ[MHCⅡ]and fibrinogen-like protein 1[FGL1]),and intracellular signaling mechanisms have substantially accelerated the development of LAG-3-targeted therapies.Multiple monoclonal antibodies against LAG-3 have entered clinical trials and have demonstrated encouraging therapeutic potential,particularly in combination with PD-1 inhibitors.This review systematically summarizes and discusses the molecular structure of LAG-3,its ligand interactions and downstream signaling pathways,as well as recent advances and future prospects in LAG-3-targeted drugs and clinical therapeutic strategies,with the aim of providing a comprehensive reference for further mechanistic studies and the optimization of future LAG-3-based immunotherapies.关键词
淋巴细胞活化基因-3/免疫检查点/肿瘤免疫疗法Key words
lymphocyte activation gene-3(LAG-3)/immune checkpoint/tumor immunotherapy分类
医药卫生引用本文复制引用
任骁华,王皞鹏..免疫检查点LAG-3的功能机制与临床应用[J].中国肿瘤生物治疗杂志,2025,32(12):1211-1220,10.基金项目
昌平实验室资助 （）
