Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer
Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer
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DOI：
10.1007/s00262-006-0228-5
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发表时间：
2007-06-01
影响因子：
5.8
通讯作者：
Levy, Frederic
中科院分区：
文献类型：
--
作者：
Alves, Pedro M. S.;Levy, Nicole;Levy, Frederic
肿瘤特异性基因产物，例如癌症/睾丸 (CT) 抗原，构成了 T 细胞疫苗开发的有希望的目标。尽管 CT 抗原经常在黑色素瘤中表达，但其在结直肠癌 (CRC) 中的表达仍知之甚少。在这里，我们研究了 CT 抗原 MAGE-A3、MAGE-A4、MAGE-A10、NY-ESO-1 和 SSX2 在 CRC 中的表达，因为它们的序列中存在明确描述的 HLA-A2 限制性表位。我们对 41 个原发性 CRC 和 14 个转移性肝脏病灶的分析证实了这些 CT 抗原的低表达频率。与原发性肿瘤相比，在转移性肿瘤中没有观察到表达频率增加。 CRC 样本的组织学分析揭示了各个 CT 抗原的异质表达。最后，可以证明自然获得的 CT 抗原特异性 CD8(+) T 细胞反应的证据。这些结果表明，部分 CRC 患者中 CT 抗原的表达诱导了易于检测的 T 细胞反应。
Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute promising targets for the development of T cell vaccines. Whereas CT antigens are frequently expressed in melanoma, their expression in colorectal cancers (CRC) remains poorly characterized. Here, we have studied the expression of the CT antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC because of the presence of well-described HLA-A2-restricted epitopes in their sequences. Our analyses of 41 primary CRC and 14 metastatic liver lesions confirmed the low frequency of expression of these CT antigens. No increased expression frequencies were observed in metastatic tumors compared to primary tumors. Histological analyses of CRC samples revealed heterogeneous expression of individual CT antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8(+) T cell response could be demonstrated. These results show that the expression of CT antigens in a subset of CRC patients induces readily detectable T cell responses.