人类白细胞抗原-E（HLA-E）在多种肿瘤中呈高表达，其与肿瘤患者预后的关系呈现肿瘤类型依赖性。HLA-E主要通过与NK细胞或T细胞上的激活性（NKG2C）或抑制性（NKG2A）受体结合，在调控抗肿瘤免疫应答中发挥重要作用。基于此，靶向 HLA-E/NKG2A 以阻断 HLA-E 与 NKG2A 的相互作用或抑制 HLA-E 表达，有望成为增强抗肿瘤免疫应答的新策略。鉴于HLA-E的功能特点设计增强型或通用型的T/NK细胞过继免疫疗法，有望提高过继免疫细胞疗法的治疗效果，具有良好的研发和临床应用前景。如何将靶向HLA-E或NKG2A的疗法与其他免疫疗法有效联合，实现更精准的免疫治疗以提高临床治疗效果是目前该方面研发和应用需要解决的难题之一。

Human leukocyte antigen-E (HLA-E) is highly expressed in many kinds of cancer and associated with the prognosis of patients in a cancer-type-dependent manner. HLA-E plays an important anti-tumor immunomodulatory role mainly by binding to activating receptor (NKG2C) or inhibitory receptor (NKG2A) on NK cells or T cells. Based on this, targeting HLA-E/NKG2A to block the interaction of HLA-E with NKG2A or inhibit HLA-E expression may be one of the promising strategies for augmenting anti-tumor immune response. Based on the functional features of HLA-E, developing enhanced or universal engineered-T/NK cells adoptive cellular immunotherapies has the potential of enhancing the therapeutic effects of adoptive cellular immunotherapies, with good prospects in research and clinical application. How to effectively combine the strategy of targeting HLA-E/NKG2A with other immune therapies for more precise immunotherapy and better clinical therapeutic effects remains one of the challenges in the research and application of anti-tumor immuotherapies.

R730.51；R730.3

国家自然科学基金面上资助项目（No. 81972719，No. 81773258，No. 81773086）；江苏省大学生创新创业训练计划基金资助项目（No. 202010313022Z）