Identification of α-fetoprotein-derived peptides recognized by cytotoxic T lymphocytes in HLA-A24+patients with hepatocellular carcinoma
Identification of α-fetoprotein-derived peptides recognized by cytotoxic T lymphocytes in HLA-A24+patients with hepatocellular carcinoma
复制标题
DOI：
10.1002/ijc.21468
复制
发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Kaneko, S
中科院分区：
文献类型：
--
作者：
Mizukoshi, E;Nakamoto, Y;Kaneko, S
甲胎蛋白（AFP）已被提出作为肝细胞癌（HCC）的基于T细胞的免疫治疗的潜在靶点，但已鉴定的其表位的数量有限，并且HCC患者中AFP特异性免疫应答的状态尚未被很好地表征。为了解决这个问题，我们研究了使用来自AFP的新型HLA-A*2402限制性T细胞表位（HLA，人类白细胞抗原）诱导AFP特异性细胞毒性T细胞（CTL）的可能性，然后分析了其发生频率与HCC患者相关临床特征之间的关系。含有HLA-A*2402结合基序并显示对HLA-A*2402的高结合亲和力的五种AFP衍生肽诱导CTL产生IFN-γ并杀死产生AFP的肝癌细胞系。AFP特异性CTL的频率为30-190/1 × 10（6）外周血单个核细胞，这与其他免疫原性癌症相关抗原衍生表位的频率相同。AFP特异性CTL应答与肝癌患者临床特征的关系分析显示，AFP表位在晚期肝癌患者中更频繁地被CTL识别，与肿瘤因素或TNM分期相关。肝癌治疗前后CTL反应的分析表明，治疗改变了AFP特异性CTL的频率。总之，我们确定了五个HLA-A*2402限制性T细胞表位来自AFP。新发现的AFP抗原表位可能是肝癌免疫治疗和分析宿主对肝癌的免疫反应的有价值的组成部分。(c)2005 Wiley-Liss，Inc.
a-Fetoprotein (AFP) has been proposed as a potential target for T-cell-based immunotherapy for hepatocellular carcinoma (HCC), but the number of its epitopes that have been identified is limited and the status of AFP-specific immunological responses in HCC patients has not been well-characterized. To address the issue, we examined the possibility of inducing AFP-specific cytotoxic T cells (CTLs) using novel HLA-A*2402-restricted T-cell epitopes (HLA, human leukocyte antigen) derived from AFP and then analyzed the relationship between its frequency of occurrence and clinical features associated with patients having HCC. Five AFP-derived peptides containing HLA-A*2402 binding motifs and showing high binding affinity to HLA-A*2402 induced CTLs to produce IFN-gamma and kill an AFP-producing hepatoma cell line. The frequency of AFP-specific CTLs was 30-190 per 1 x 10(6) peripheral blood mononuclear cells, which was the same as that of other immunogenic cancer associated antigen-derived epitopes. Analyses of the relationships between AFP-specific CTL responses and clinical features of patients with HCC revealed that AFP epitopes were more frequently recognized by CTLs in patients with advanced HCC correlating to tumor factors or the stage of TNM classification. The analyses of CTL responses before and after HCC treatments showed that the treatments changed the frequency of AFP-specific CTLs. In conclusion, we identified five HLA-A*2402-restricted T-cell epitopes derived from AFP. The newly identified AFP epitopes could be a valuable component of HCC immunotherapy and for analyzing host immune responses to HCC. (c) 2005 Wiley-Liss, Inc.