非小细胞肺癌患者癌胚抗原特异性细胞毒T细胞与临床疗效的研究

目的 通过对HLA-A0201限制性的特异性细胞毒T细胞(CTL)分析,研究晚期非小细胞肺癌患者化疗不同疗效与T淋巴细胞对特异性抗原表位免疫应答的差异.方法 鉴定HLA-A0201阳性的晚期非小细胞肺癌患者13例(Ⅲb期6例,Ⅳ期7例);给予吉西他滨+顺铂方案化疗,收集化疗前患者的外周血单个核细胞,采用酶联免疫斑点试验测定针对癌胚抗原表位肽的特异性CTL的数量和功能.结果 晚期非小细胞肺癌化疗有效患者外周血癌胚抗原(CEA)多肽特异性CTL数量和功能明显高于晚期非小细胞肺癌化疗无效患者.结论 肺癌特异性表位的CTL应答,在不同化疗疗效患者的应答特征不同.化疗有效的患者特异性CTL应答水平显著高于疗效无效者,肺癌特异性CTL应答与临床疗效有密切关系.肺癌特异性CTL在抑制肿瘤的过程中发挥着重要作用,这将有助于预测肺癌患者的临床转归和开拓肺癌的免疫治疗的新策略.

Detection of carcino-embryonic antigen-specific cytotoxic lymphocytes and their association with clinical therapy in patients with non-small cell lung carcinoma

Objective To investigate the difference of host immune response specific to non-small cell lung carcinoma（NSCLC） between different clinical chem-curative effect by quantitative analysis of HLA-A0201 restricted antigen-specific cytotoxic T lymphocyte cells（CTL）.Methods The frequency of carcino-embryonic antigen-specific CTL cells in the peripheral blood mononuclear cells from 13 patients with NSCLC were quantified by enzyme-linked immunospot assays using three HLA-A0201 restricted carcino-embryonic antigen（CEA） epitopes（6 cases with phrase Ⅲb,7 cases with phrase Ⅳ）.The chemotherapy consisted of gemcitabine and cisplatin.Results High frequencies of circulating antigen-specific CTL cells were detected in most individuals with effective chemotherapy.Antigen-specific CTL cells were not detected in the peripheral blood mononuclear cell from individuals with inefficient chemotherapy.Conclusion CEA-specific CTL cells may play a crucial role in complete clearance of tumor from patients with NSCLC.The proposed function of CEA-specific CTL may provide an important approach to the treatment for NSCLC.