Correa Isabel, Plunkett Timothy, Coleman Julia, Galani Eleni, Windmill Elisabeth, Burchell Joy M, Taylor-Papdimitriou Joyce
Breast Cancer Biology Group, Cancer Research UK, Guy's Hospital, London, United Kingdom.
Int J Cancer. 2005 Jul 10;115(5):760-8. doi: 10.1002/ijc.20949.
The epithelial mucin MUC1 is one of the few tumour-associated antigens identified for breast cancer. Several MUC1-derived peptides binding HLA-A0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA-A0201-binding peptide has been identified in a human system. We have evaluated the CD8(+) T-cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8(+) T-cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA-A0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA-A0201(+) breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system.
上皮黏蛋白MUC1是已确定的少数几种乳腺癌相关肿瘤抗原之一。已鉴定出几种与HLA-A0201分子结合的源自MUC1的肽段，它们对应于串联重复序列之外的序列。用其中一些肽段进行免疫可在小鼠中诱导保护性抗肿瘤免疫。在人体系统中也鉴定出了另一种与HLA-A0201结合的肽段。我们使用乳腺癌患者和正常供体的外周血淋巴细胞评估了对所有这些肽段的CD8(+) T细胞反应。针对其中一些肽段可在体外产生特异性CD8(+) T细胞反应，但仅在经过几轮体外再刺激后才会出现，并且它们无法识别内源性表达该抗原的人类细胞。尽管如此，在一些HLA-A0201(+)乳腺癌患者的外周血中可检测到被携带来自信号序列（LLLLTVLTV）的肽段的HLA-A0201四聚体识别的T细胞，而在健康成年人中则未检测到。该肽段是所测试的肽段中唯一在人体系统中鉴定出的，这些结果强调了将数据从实验动物模型转化到人体系统中所涉及的潜在问题。
