食管鳞癌NY-ESO-1、SSX-2和MAGE-A3的特异性CTL免疫反应

Analysis of NY-ESO-1,SSX-2 and MAGE-A3 specific CTL immune response in esophageal squamous cell carcinoma

目的探讨食管鳞癌患者肿瘤特异性抗原(TSA)中纽约食管鳞状上皮癌抗原1(NY-ESO-1)、滑膜肉瘤X断裂点基因2(SSX-2)和黑色素瘤抗原A3(MAGE-A3)的特异性CTL免疫应答差异及其临床相关性及其在食管癌免疫治疗中的应用价值。方法收集51例新疆医科大学附属肿瘤医院2015年4月-2016年10月确诊食管鳞癌初治患者,用合成的NY-ESO-1、SSX-2和MAGE-A3特异性CTL抗原表位肽刺激食管鳞癌患者的外周血单个核细胞(PBMCs),采用酶联免疫斑点法(ELISPOT)检测分泌γ-干扰素(IFN-γ)的CTL细胞频率及强度,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NY-ESO-1、SSX-2和MAGE-A3特异性CTL反应频率分别为19.6%(10/51)、9.8%(5/51)和15.7%(8/51),反应强度分别为36.33、36.00和45.83SFC/106 PBMCs;其三者的特异性CTL反应频率及强度在食管鳞癌临床特征中的差异均无统计学意义(P>0.05)。结论食管鳞癌患者可对肿瘤特异性抗原NY-ESO-1、SSX-2和MAGE-A3多肽产生特异性T细胞免疫反应,是否可作为食管癌免疫治疗靶点的指标尚需进一步研究。

Objective To investigate the specific cytotoxic T lymphocyte cells （CTL） immune response and its clinical correlation and prognosis on New York esophageal squamous cell carcinoma （ESCC） antigen 1 （NY-ESO-1）, synovial sarcoma X break point gene 2 （SSX-2） and melanoma-associated antigen A3 （MAGE-A3） in tumor-specific antigen （TSA） in patients with ESCC, and explore its application value in immunotherapy of esophageal carcinoma. Methods A total of 51 patients diagnosed as ESCC from April 2015 to October 2016 in The Affiliated Tumor Hospital of Xinjiang Medical University were collected. NY-ESO-1, SSX-2, MAGE-A3-specific CTL epitope peptides were used to stimulate peripheral blood mononuclear cells （PBMC） of patients with ESCC. 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 and prognosis of patients with ESCC was analyzed. Results （1） The frequency of NY-ESO-1, SSX-2 and MAGE-A3-specific CTL reactions in peripheral blood of patients with ESCC was 19.6% （10/51）, 9.8% （5/51） and 15.7% （8/51）, and the response intensity was 36.33 SFC/10＋6 PBMCs, 36.00 SFC/10＋6 PBMCs and 45.83 SFC/10＋6 PBMCs; （2） There was no significant difference in the frequency and intensity of specific CTL reaction among the three groups in the clinical features of ESCC （P 〉0.05）. Conclusion The patients with ESCC can produce specific T cell immunoreactivity on TSA： NY-ESO-1, SSX-2 and MAGE-A3 polypeptides, whether it can be used as a target for immunotherapy of esophageal cancer needs further study.