目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌（HNSCC）的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗（化疗）对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A（KLRC1）主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E（P<0.01）,与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关（P<0.01）。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平（P<0.01）;化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用（P=0.013）。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。

Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma（HNSCC）．Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases．The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry．Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel．Results NKG2A（KLRC1）was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes．The high expression of NKG2A/HLA-E in HNSCC tumors（P<0.01）were closely related to poor prognosis．NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints（P<0.01）．Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes（P<0.01）．Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC（P=0.013）．Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC．

肿瘤免疫治疗是指利用人体的免疫机制,通过主动或被动的方法增强患者免疫功能,达到杀伤肿瘤细胞的目的。嵌合抗原受体T细胞（CAR-T）作为肿瘤免疫治疗的新型精准靶向疗法,近几年通过优化和改良已成功应用于多种血液肿瘤的治疗,是目前恶性肿瘤治疗中最有潜力的疗法之一。但由于实体瘤中存在显著的异质性和复杂的肿瘤免疫微环境,CAR-T在实体瘤中的应用仍面临诸多挑战。本文将对目前 CAR-T 细胞治疗实体瘤的研究成果、现存挑战及相应的优化策略进行综述,以期为后续 CAR-T 细胞治疗实体肿瘤研究提供参考。

Tumor immunotherapy is the process of enhancing patients’ immune system through active or passive methods to achieve the goal of eliminating tumor cells．Through optimization and modification,chimeric antigen receptor T cells（CAR-T）,a novel precise targeted therapy of cancer immunotherapy,have been successfully used in the treatment of several hematological malignancies in recent years．CAR-T is considered as one of the most promising therapies for the treatment of malignant tumors at the moment．However,application of CAR-T in solid tumors still confronts several difficulties due to the high heterogeneity and intricate tumor immune microenvironment．To serve as a reference for future CAR-T cell therapy for solid tumors,the present research findings,current difficulties and associated optimization techniques are reviewed in this paper．