Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma
Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma
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DOI：
10.1016/s0168-8278(03)00484-7
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发表时间：
2004-01-01
影响因子：
25.7
通讯作者：
Missale, G
中科院分区：
文献类型：
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作者：
Zerbini, A;Pilli, M;Missale, G
背景/目标：黑色素瘤抗原编码基因家族的成员在不同组织学类型的肿瘤中表达，但在正常组织中不表达。方法：在本研究中，我们分析了法师-1和-3基因在肝细胞癌（HCC）组织中的表达，以及对法师-1和-3的HLA-A1和-A2限制性表位特异的循环和肿瘤浸润的CD 8+细胞的频率、表型和功能。我们的研究第一次显示了在HCC患者的肿瘤组织中存在法师/四聚体+CD 8细胞。这些细胞能够识别法师-1序列161-169和法师-3序列271-279。在具有特别高频率的法师-1序列161-169特异性T细胞的患者中，进行表型和功能分析，显示最近引发的CD 8细胞的表型（CD28 + CD27 + CD45RA-CCR7）。观察到法师-MAGE-1的自发体内引发。HCC患者中特异性T细胞应答和法师抗原在该肿瘤中的高频率表达，使得该抗原成为肝细胞癌中MAGE特异性免疫疗法的潜在候选者。(C)2003年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Members of the melanoma antigen encoding gene family are expressed in tumors of different histological types but not in normal tissue. For this reason, they are attractive targets for cancer immunotherapy.Methods: In the present study, we analyzed the expression of MAGE-1 and -3 genes in the hepatocellular carcinoma (HCC) tissue as well as frequency, phenotype and function of circulating and tumor infiltrating CD8 + cells specific for HLA-A1 and -A2 restricted epitopes of MAGE-1 and -3.Results: Our study shows for the first time the presence of MAGE/tetramer + CD8 cells in the tumor tissue of patients with HCC. These cells are able to recognize the MAGE-1 sequence 161-169 and the MAGE-3 sequence 271-279. In a patient with a particularly high frequency of MAGE-1 sequence 161-169-specific T cells, phenotypic and functional analysis was performed showing a phenotype of recently-primed CD8 cells (CD28 + CD27 + CD45RA - CCR7).Conclusions: The observation of a spontaneous in vivo priming of a MAGE-specific T cell response in patients with HCC and the high frequency of MAGE antigens expression in this tumor, makes this antigen a potential candidate for a MAGE-specific immunotherapy in hepatocellular carcinoma. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.