化疗联合NKG2A抑制剂抗头颈部鳞状细胞癌作用的研究  

Effect of chemotherapy combined with NKG2A inhibitor on head and neck squamous cell carcinoma

作　　者：方喜生 刘霞 王秀艳 彭倩 吕琳 刘国龙 FANG Xisheng;LIU Xia;WANG Xiuyan;PENG Qian;LV Lin;LIU Guolong(Department of Medical Oncology,Second Affiliated Hospital,School of Medicine,South China University of Technology(Guangzhou First People’s Hospital),Guangzhou 510180,China)

机构地区：[1]华南理工大学附属第二医院(广州市第一人民医院)肿瘤科,广东广州510180

出　　处：《广州医药》2024年第8期860-868,共9页Guangzhou Medical Journal

基　　金：广东省医学科研基金面上项目(B2021023);广州市科技局基础与应用基础研究一般项目(202102080609)。

摘　　要：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.

关 键 词：头颈部鳞状细胞癌 NKG2A抑制剂 化疗 抗肿瘤作用 

分 类 号：R739.91[医药卫生—肿瘤]