鼻咽癌MAGE-A1、MAGE-A3特异性CTL免疫应答差异与临床相关性

Correlation Clinical and Difference of Nasopharyngeal Carcinoma MAGE-A1 and MAGE-A3 Specific CTL Immune Responses

目的通过观察肿瘤特异性抗原(TAA)中黑色素瘤抗原A1(MAGE-A1)、黑色素瘤抗原A3(MAGE-A3)抗原表位肽刺激外周血单个核细胞(PBMC)中特异性细胞毒性T细胞(CTL)产生γ干扰素(IFN-γ)的能力,分析鼻咽癌患者的特异性CTL免疫应答差异及其临床相关性。方法收集66例新疆医科大学附属肿瘤医院2015年3月至2016年6月确诊鼻咽癌住院患者。用合成的MAGE-A1、MAGE-A3特异性CTL抗原表位肽刺激鼻咽癌患者的PBMC,采用酶联免疫斑点法(ELISPOT)检测分泌IFN-γ的CTL细胞的频率及强度。并分析其与鼻咽癌患者临床特征(性别、年龄、民族、TNM分期)之间的关系。结果 ELISPOT检测结果:(1)鼻咽癌患者外周血中MAGE-A1、MAGE-A3特异性CTL免疫应答阳性率分别为34.7%和22.2%,平均反应强度分别35.0和40.0 SFC/106PBMC。(2)鼻咽癌MAGE-A1特异性抗原多肽反应阳性率在性别、年龄、民族、TNM分期无统计学差异。MAGE-A1平均反应强度:女性组MAGE-A1平均反应强度为50.0 SFC/106PBMC,明显高于男性组32.8 SFC/106PBMC(P=0.044)。(3)鼻咽癌患者MAGE-A3特异性抗原多肽反应阳性率在临床特征间无明显差异。MAGE-A3平均反应强度:汉族组43.3 SFC/106PBMC明显高于维族组21.6 SFC/106PBMC(Ρ=0.031),Ⅲ期组49.5SFC/106PBMC明显高于Ⅳ组26.6 SFC/106PBMC(P=0.018)。结论鼻咽癌患者可对肿瘤特异性抗原MAGE-A1、MAGE-A3多肽产生特异性T细胞免疫反应,为鼻咽癌免疫治疗研究提供线索。

Objective To investigate the ability of secreting interferon- γ （IFN-γ ） of the peripheral blood monocular cells（PBMC） stimulated MAGE-A1 ,MAGE-A3 specific cytotoxic T lymphocyte （CTL） epitopes peptides and to analyze the difference of CTL immune response in patients with NPC and their clinical significance. Methods 66 NPC patients were enrolled into the study in Xinjiang Tumor hospital from March 2015 to June 2016. The MAGE-A1,MAGE-A3 overlapping peptides were synthetized to use. The IFN-gamma released Elispot assay was employed to detect the MAGE-A1/MAGE-A3 specific T cell. The correlation of clinicopathological characteristics （ethnic ,gender,age,primary TNM stage） with CTL were evaluated. Results （1） The recognized frequency of MAGE-A1 MAGE-A3 speeifie T cell response in patients with NPC were 34.7 % and 22.2 %. The magnitudes of them were 35.0and 40.0 SFC/106PBMC. （2） The magnitude of specific T cell response inducing MAGE-A1 peptides in female group was 50SFU/106PBMCs, was higher than that in male group （32,8SFU/106）PBMCs. The difference were significant （P = 0.044）.（3） The magnitude of specific T cell response inducing MAGE-A3 peptides in Han group was 43.4SFU/106PBMCs, was higher than that Uyghur group（21.6SFU/106PBMCs）. The difference was significant （P = 0.031）. And this number of stage Ⅲ group was 49.5 SFC/106PBMC whiehg higher than that 1Vgroup （261.6SFU/106PBMCs）. The difference was significant （P = 0.018）. Conclusion MAGE-A1 ,MAGE-A3 T cell responses might give a clue to be a new target for immune therapy in NPC in the future.