Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients
Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients
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DOI：
10.1002/ijc.27359
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发表时间：
2012-09-01
影响因子：
6.4
通讯作者：
Nakayama, Eiichi
中科院分区：
文献类型：
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作者：
Ohue, Yoshihiro;Eikawa, Shingo;Nakayama, Eiichi
分析了非小细胞肺癌（NSCLC）患者对XAGE-1b（GAGED 2a）的自发免疫应答。在10%（20/200）的NSCLC患者和19%（13/69）的IIIB/IV期肺腺癌患者中观察到抗XAGE-1b（GAGED 2a）的抗体应答。在检查的XAGE-1b（GAGED 2a）抗体阳性患者中，88%（14/16）检测到CD 4 T细胞应答，67%（6/9）检测到CD 8 T细胞应答。XAGE-1b（GAGED 2a）抗体阳性患者中频繁的抗体应答以及CD 4和CD 8 T细胞应答表明XAGE-1b（GAGED 2a）抗原在NSCLC患者中具有强免疫原性。我们从抗体阳性患者的PBMC中建立了T细胞克隆，并将DRB 1 *04：05限制性XAGE-1b（GAGED 2a）1831肽（14聚体）确定为CD 4 T细胞表位，将A*02：06限制性XAGE-1b（GAGED 2a）21-29肽（9聚体）确定为CD 8 T细胞表位。至于肽识别，CD 4和CD 8 T细胞克隆对天然加工的抗原有应答。CD 4 T细胞克隆识别用合成蛋白或来自XAGE-1b转染的293 T细胞的裂解物脉冲的DC。CD 8 T细胞克隆对表达XAGE-1b（GAGED 2a）和适当的HLA I类等位基因的肿瘤显示出细胞毒性。这些发现确立了XAGE-1b（GAGED 2a）作为肺癌疫苗的有希望的靶点。
The spontaneous immune responses against XAGE-1b (GAGED2a) were analyzed in non-small cell lung cancer (NSCLC) patients. An antibody response against XAGE-1b (GAGED2a) was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma patients. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b (GAGED2a) antibody-positive patients examined. Frequent antibody responses and CD4 and CD8 T-cell responses in XAGE-1b (GAGED2a) antibody-positive patients indicate the strong immunogenicity of the XAGE-1b (GAGED2a) antigen in NSCLC patients. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b (GAGED2a) 1831 peptide (14-mer) as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b (GAGED2a) 21-29 peptide (9-mer) as a CD8 T cell epitope. As for peptide recognition, CD4 and CD8 T-cell clones responded to naturally processed antigen. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein or a lysate from XAGE-1b-transfected 293T cells. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b (GAGED2a) and the appropriate HLA class I allele. These findings establish XAGE-1b (GAGED2a) as a promising target for a lung cancer vaccine.