Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Immunol. 2021 Jan 8;11:563258. doi: 10.3389/fimmu.2020.563258. eCollection 2020.
Although various immunotherapies have exerted promising effects on cancer treatment, many patients with cancer continue to exhibit poor responses. Because of its negative regulatory effects on T cells and its biological functions related to immune and inflammatory responses, there has been considerable emphasis on a protein-coding gene named lymphocyte-activation gene 3 (LAG3). Recently, evidence demonstrated marked synergy in its targeted therapy with programmed death-1 and programmed death-1 ligand-1 (PD-1/PD-L1) blockade, and a variety of LAG3 targeted agents are in clinical trials, indicating the important role of LAG3 in immunotherapy. This mini-review discusses preclinical and clinical studies investigating PD-1 pathway blockade in combination with LAG3 inhibition as a potentially more effective immunotherapy strategy for further development in the clinic. This strategy might provide a new approach for the design of more effective and precise cancer immune checkpoint therapies.
虽然各种免疫疗法在癌症治疗方面已经取得了有希望的效果，但许多癌症患者仍然表现出较差的反应。由于其对 T 细胞的负向调节作用及其与免疫和炎症反应相关的生物学功能，一种名为淋巴细胞激活基因 3（LAG3）的蛋白编码基因受到了相当大的关注。最近的证据表明，其与程序性死亡受体 1 和程序性死亡受体配体 1（PD-1/PD-L1）阻断的靶向治疗具有显著的协同作用，并且多种 LAG3 靶向药物正在临床试验中，表明 LAG3 在免疫治疗中的重要作用。这篇迷你综述讨论了 PD-1 通路阻断联合 LAG3 抑制作为一种更有效的免疫治疗策略的临床前和临床研究，以进一步在临床上开发。这种策略可能为设计更有效和精确的癌症免疫检查点治疗提供一种新方法。
