中晚期癌症患者使用抗PD-1单抗治疗前后外周血淋巴细胞刺激性免疫检查点GITR和OX40的变化及与疗效的关系  

Relationship between changes in expression of GITR and OX40 on PBMCs with immunotherapy response in intermediate and advanced cancer

作　　者：杜无双 胡毅[1] DU Wushuang;HU Yi(Department of Medical Oncology, Chinese PLA General Hospital, Beijing 100853, China)

机构地区：[1]解放军总医院肿瘤内科,北京100832

出　　处：《解放军医学院学报》2018年第4期308-311,共4页Academic Journal of Chinese PLA Medical School

摘　　要：目的探究中晚期肿瘤患者接受抗PD-1单抗治疗前后刺激性免疫检查点的表达变化及与疗效的关系。方法选取2016年12月-2017年8月于本院接受抗PD-1单抗治疗的中晚期癌症患者21例,于每次免疫治疗前采集静脉血5 ml,每人至少接受2次治疗,分别于每次治疗前采血。通过流式细胞仪检测OX40和GITR在T淋巴细胞上的表达,分析其变化与疗效的关系。治疗后通过RECIST1.1两周期(每周期21 d)疗效评价,将患者分为有效组(16例)和无效组(5例),比较两组OX40和GITR的表达差异。结果 21例晚期癌症患者中,男性16例,女性5例;年龄39~81岁,平均年龄58岁。其中肺癌15例,食管癌2例,宫颈癌2例,尿道肿瘤2例。第二次免疫治疗后,在CD4+T淋巴细胞、CD8+T淋巴细胞和NK细胞上,治疗无效组GITR的表达均显著高于有效组(P=0.007、0.007、0.002)。无效组OX40在CD4+T淋巴细胞中的表达显著高于有效组(P=0.039)。结论中晚期癌症患者接受PD-1单抗治疗后外周血刺激性免疫检查点表达发生变化,且治疗有效与无效组间GITR表达差异显著,可能成为PD-1单抗早期疗效评价指标。Objective To find out the relationship between clinical efficacy and changes in co-stimulatory immune biomarkers on peripheral blood monocular cells（PBMCs） in intermediate and advanced cancer patients undergoing anti PD-1 monoclonal antibody treatment. Methods Twenty-one patients diagnosed as intermediate and advanced cancer received nivolumab or pembrolizumab in Chinese PLA General Hospital from December 2016 to August 2017 were selected. Every patient received at least two cycles of treatment, and 5 ml venous blood was collected before each treatment. Flow cytometry analysis was used to test the expression of OX40 and GITR on T lymphocyte, and the relationship between their changes and clinical efficacy was analyzed. The treatment lasted for two cycles（21 day per cycle）. After treatment, according to the RECIST1.1 standard, patients were divided into response group（n=16） and non-response group（n=5）. The differences of expression of OX40 and GITR were compared between two groups. Results Of the 21 cases, there were 16 males and 5 females with mean age of 58 years（ranging from 39 to 81 years）. Fifteen cases had lung cancer, 2 cases had esophageal cancer, 2 cases had cervical cancer and 2 cases had urethra tumor. After the second cycle of immunotherapy, the expressions of GITR on CD4＋ lymphocyte, CD8＋ T lymphocyte and NK cells in non-response group were significantly higher than those of response group（P=0.007, 0.007, 0.002, respectively）, and the expression of OX40 on CD4＋lymphocyte of non-response group was significantly higher than that of response group（P=0.039）. Conclusion The expressions of co-stimulatory immune biomarkers on PBMCs has changed in intermediate and advanced cancer patients undergoing anti PD-1 monoclonal antibody treatment, and GITR in responsive patients is significantly different with that in nonresponsive patients, which may be an index to predict outcomes of immunotherapy.

关 键 词：免疫治疗 PD-1单抗 免疫检查点 疗效 

分 类 号：R734.2[医药卫生—肿瘤]