Wei Yiming, Li Zhaoming
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2022 Apr 14;12:831407. doi: 10.3389/fonc.2022.831407. eCollection 2022.
Although PD-1 blockade therapy has been promising in cancer treatment, only 4% (pancreatic cancer) to 70% (melanoma) of patients have a positive response to this blockade therapy, which is one of its important disadvantages. Therefore, it is important to seek out new targets for cancer immunotherapy to improve the overall response rate in patients. Lymphocyte activation gene-3 (LAG-3), an immune checkpoint receptor, is mainly expressed in activated immune cells. LAG-3 maintains the body's immune homeostasis under physiological conditions while mediating tumour immune escape. Several preclinical and clinical examinations have shown that LAG-3 blockade effectively alleviates the patient's tolerance to PD-1 immune checkpoint inhibitors. Moreover, the combination of LAG-3 and PD-1 blockade has good clinical efficacy in cancers. Hence, synchronous LAG-3 and PD-1 inhibition may be a potential new strategy for tumour immunotherapy.
尽管PD-1阻断疗法在癌症治疗中前景广阔,但只有4%(胰腺癌)至70%(黑色素瘤)的患者对这种阻断疗法有阳性反应,这是其重要缺点之一。因此,寻找癌症免疫治疗的新靶点以提高患者的总体反应率很重要。淋巴细胞激活基因-3(LAG-3)是一种免疫检查点受体,主要表达于活化的免疫细胞中。LAG-3在生理条件下维持机体免疫稳态,同时介导肿瘤免疫逃逸。多项临床前和临床检查表明,LAG-3阻断可有效减轻患者对PD-1免疫检查点抑制剂的耐受性。此外,LAG-3与PD-1阻断联合在癌症治疗中具有良好的临床疗效。因此,同步抑制LAG-3和PD-1可能是肿瘤免疫治疗的一种潜在新策略。