Laboratory for Molecular and Cellular Therapy (LMCT), Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Nuclear Medicine Department, UZ Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium.
Int J Mol Sci. 2020 Dec 23;22(1):75. doi: 10.3390/ijms22010075.
The blockade of immune checkpoints (ICPs), such as cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed death-1 (PD-1) and its ligand (PD-L1), has propelled the field of immuno-oncology into its current era. Drugs targeting these ICPs have improved clinical outcome in a number of patients with solid and hematological cancers. Nonetheless, some patients have no benefit from these ICP-blocking therapies. This observation has instigated research into alternative pathways that are responsible for the escape of cancer cells from anti-cancer immune responses. From this research, a number of molecules have emerged as promising therapeutic targets, including lymphocyte activating gene-3 (LAG-3), a next-generation ICP. We will review the current knowledge on the biological activity of LAG-3 and linked herewith its expression on activated immune cells. Moreover, we will discuss the prognostic value of LAG-3 and how LAG-3 expression in tumors can be monitored, which is an aspect that is of utmost importance, as the blockade of LAG-3 is actively pursued in clinical trials.
免疫检查点（ICPs）的阻断，如细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）和程序性死亡受体 1（PD-1）及其配体（PD-L1），推动了肿瘤免疫治疗进入当前时代。针对这些 ICP 的药物改善了许多实体瘤和血液系统癌症患者的临床结局。然而，一些患者并没有从这些 ICP 阻断治疗中获益。这一观察结果促使研究人员寻找导致癌细胞逃避抗癌免疫反应的其他途径。从这项研究中，出现了一些有前途的治疗靶点，包括淋巴细胞激活基因 3（LAG-3），这是一种新一代的 ICP。我们将回顾 LAG-3 的生物学活性及其在激活免疫细胞上的表达的相关知识。此外，我们将讨论 LAG-3 的预后价值，以及如何监测肿瘤中的 LAG-3 表达，这是一个非常重要的方面，因为 LAG-3 的阻断正在临床试验中积极探索。
