食管鳞癌SALL4和MAGE-A1的特异性免疫反应  

Analysis of SALL4 and MAGE-A1 specific cytotoxic T cell(CTL) immune response in esophageal carcinoma

作　　者：冯亚宁 张典刚[2] 闫超 王若峥 FENG Yaning;ZHANG Diangang;YAN Chao;WANG Ruozheng(Key Laboratory of Cancer Immunology and Radiotherapy,Chinese Academy of Medical Science,Urumqi 830011,China;Department of Radiation Oncology,Affiliated Tumor Hospital,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]中国医学科学院肿瘤免疫与放疗研究重点实验室,乌鲁木齐830011 [2]新疆医科大学附属肿瘤医院放疗中心,乌鲁木齐830011

出　　处：《新疆医科大学学报》2018年第8期933-937,942,共6页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(U1603282);中国医学科学院肿瘤免疫研究和放疗研究重点实验室专项课题(2017PT31043)

摘　　要：目的检测食管鳞癌患者婆罗双树样基因4(SALL4)和黑色素瘤抗原A1(MAGE-A1)特异性细胞免疫水平,探讨其患者的特异性免疫应答及其与临床特征的相关性,为食管鳞癌的临床免疫治疗潜在靶点的选择提供实验依据。方法收集2015年4月-2016年10月新疆医科大学附属肿瘤医院放疗中心收治的食管鳞癌初治患者51例,用合成的肿瘤睾丸抗原(CTA)中的SALL4和MAGE-A1特异性抗原表位肽刺激患者外周血单个核细胞(PBMC),采用酶联免疫斑点法(ELISPOT)检测分泌γ干扰素(IFN-γ)细胞的频率及强度,并分析其与食管鳞癌患者临床特征的关系。结果食管鳞癌患者外周血中,SALL4和MAGE-A1特异性CTL反应频率分别为29.4%(15/51)和27.5%(14/51),反应强度分别为78.0、55.7SFC/106 PBMCs;N0~1组MAGE-A1特异性CTL反应频率(37.5%)明显高于N2~3组(10.5%)(P=0.037);SALL4特异性CTL免疫反应频率与MAGE-A1呈现弱的正相关性(r=0.471,P=0.000)。结论食管鳞癌患者可对肿瘤特异性抗原SALL4和MAGE-A1多肽产生特异性T细胞免疫反应,并可为食管鳞癌免疫治疗的临床应用提供线索。Objective To investigate the level of SALL4 and MAGE-A1 specific immune response in the patients with esophageal cancer to explore its application value in immunotherapy of esophageal carcinoma.Methods A total of 51 patients diagnosed with esophageal carcinoma from April 2015 to October 2016 in The Affiliated Tumor Hospital of Xinjiang Medical University were collected.Sythesized cancer-testis antigen（CTA）SALL4-and MAGE-A1-specific CTL epitope peptides were used to stimulate peripheral blood mononuclear cells of patients.The frequency and intensity of CTL cells secreting interferon-γ（IFN-γ）were detected by ELISPOT,and its relationship between CTL cells and clinical features of patients with esophageal cancer was analyzed.Results The response frequency of SALL4-and MAGE-A1-specific CTL in peripheral blood of patients with esophageal cancer was 29.4%（15/51）and 27.5%（14/51）,and the reaction intensity was 78.0 and 55.7 SFC/106（PBMCs）,respectively;the response frequency of MAGE-A1 specific CTL in N0~1 group（37.5%）was significantly higher than that in N2~3 group（10.5%）,and the difference was statistically significant（P = 0.037）;the frequency of SALL4-specific T cell response was mildly associated with MAGE-A1（r=0.471,P =0.000）.Conclusion The patients with esophageal carcinoma can produce specific T cell immunoreactivity on cancer-specific antigen SALL4 and MAGE-A1,which could provide clues for immunotherapy of esophageal cancer.

关 键 词：食管鳞癌 T细胞免疫 酶联免疫斑点法 肿瘤睾丸抗原 

分 类 号：R735.1[医药卫生—肿瘤]