自然杀伤细胞2 族成员A（NKG2A）为免疫细胞表面重要的免疫检查点，NKG2A 与其配体HLA-E 的结合会抑制NK 细胞和T 细胞的免疫效应功能，甚至使之发生功能耗竭，导致肿瘤细胞免疫逃逸。抗NKG2A 抗体可以通过阻断NKG2A 与其配 体的结合而恢复NK 细胞和T 细胞的功能，从而唤醒强大的抗肿瘤免疫。与其他免疫检查点（如PD-1、CTLA-4 等）相比，NKG2A 阻断性抗体在临床肿瘤治疗中具有其独特的优势，其阻断NKG2A 的识别及其信号通路，能够同时逆转T 细胞和NK 细胞的功能 耗竭，全面唤醒机体的抗肿瘤效应。基于NKG2A 的抗肿瘤免疫疗法正在开展多项临床试验，显示出良好的安全性和有效性。本 文就NKG2A 及其配体的表达与信号转导、NKG2A 介导免疫细胞的功能耗竭，以及目前以NKG2A 为靶点的肿瘤免疫治疗策略和 临床研究进展现状、存在问题和对策进行阐述，为以NKG2A 为靶点的肿瘤免疫治疗策略的开发和临床应用提供参考。

Natural killer group 2 member A (NKG2A) is an important immune checkpoint molecule on the surface of immune cells. The binding between NKG2A and its ligand HLA-E inhibits the immune function of NK cells and T cells, and even causes their functional exhaustion and leads to tumor escape. Anti-NKG2A antibody can restore the function of T cells and NK cells by blocking the binding of NKG2A to its ligand, thus awakening a strong antitumor efficacy. Compared with other immune checkpoint molecules, such as PD-1 and CTLA-4, NKG2A-blocking antibody has unique advantages in clinical oncology treatment. It blocks the identification of NKG2A and relevant signaling pathways and reverses the functional exhaustion of T cells and NK cells at the same time, fully awakening the strong anti-tumor immunity of the body. Currently, several clinical trials on NKG2A-based anti-tumor immunotherapy are ongoing, showing good safety and therapeutic efficacy. In this review, we summarize the expression and signal transduction of NKG2A and HLA-E, NKG2A-mediated functional exhaustion of immune cells, and current clinical research status, problems, and possible strategies of NKG2A-targeted tumor immunotherapy, to provide a reference for the development and clinical application of NKG2A-targeted tumor immunotherapy.

国家自然科学基金资助项目（No. 91842305, No. 81771686）；山东省重点研发计划（重大科技创新工程）资助项目（No. 2019JZZY021013）