Shan Chanchan, Li Xing, Zhang Jian
Department of Cardiology, Wuxi No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China.
Department of Orthopaedic Surgery, Wuxi No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China.
Oncol Lett. 2020 Nov;20(5):207. doi: 10.3892/ol.2020.12070. Epub 2020 Sep 8.
Immune checkpoint inhibition has been shown to successfully reactivate T cell responses directed against tumor-associated antigens, resulting in significantly prolonged overall survival in patients with various types of solid tumors. Among them, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) play key roles in tumor immune escape and are well-established targets of cancer immunotherapy. However, the low response rate PD-1 and CTLA-4 is a limitation and a challenge. Hence, studies have focused on investigating the tumor microenvironment for alternative therapeutic targets. Lymphocyte activation gene 3 protein (LAG-3) negatively regulates T lymphocytes by binding to the extracellular domain of the ligand, thus avoiding autoimmunity caused by T cell overactivation. LAG-3 is an important immune checkpoint and plays a balanced regulatory role in the human immune system. LAG-3 is now regarded as a new generation of immunotherapy targets. The present review describes the research progress of LAG-3 to provide reference for further investigation of LAG-3. The immune checkpoint of LAG-3 plays a crucial role in cancer development and may be used in future clinical practice of cancer therapy.
免疫检查点抑制已被证明能成功重新激活针对肿瘤相关抗原的T细胞反应,从而显著延长各种实体瘤患者的总生存期。其中,细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)在肿瘤免疫逃逸中起关键作用,是成熟的癌症免疫治疗靶点。然而,PD-1和CTLA-4的低应答率是一个限制和挑战。因此,研究集中在探索肿瘤微环境以寻找替代治疗靶点。淋巴细胞激活基因3蛋白(LAG-3)通过与配体的胞外域结合来负向调节T淋巴细胞,从而避免T细胞过度激活引起的自身免疫。LAG-3是一个重要的免疫检查点,在人类免疫系统中发挥平衡调节作用。LAG-3现在被视为新一代免疫治疗靶点。本综述描述了LAG-3的研究进展,为进一步研究LAG-3提供参考。LAG-3的免疫检查点在癌症发展中起关键作用,可能用于未来癌症治疗的临床实践。