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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen
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Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen

机译：接种了MAGE抗原的黑色素瘤患者的肿瘤消退与T细胞反应之间的相关性

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The cancer-germline gene MAGE-3 codes for tumor-specific antigens recognized on many tumors by T lymphocytes. A MAGE-3 antigen presented by HLA-A1 has been used in several vaccination trials on metastatic melanoma patients. Only a small minority of patients have shown evidence of tumor regression. Attempts to correlate the tumor rejections with the cytotoxic T lymphocyte (CTL) response against the vaccine have been hampered by the low level of these responses. In noncancerous individuals, the frequency of the T cell precursors against antigen MAGE-3.A1 is ≈4 x 10~(-7) CD8 T cells. The diversity of the T cell receptor repertoire of these anti-MAGE-3.A1 precursors was analyzed in one individual. The results indicate that it is very likely that the repertoire comprises >100 clonotypes. On this basis, it is possible to use not only the frequency of CTL precursors in the blood but also the presence of dominant clonotypes to ascertain in patients the existence of anti-MAGE-3.A1 responses as low as 10~(-6) of CD8. With this approach, we observed a correlation between tumor regression and anti-MAGE-3.A1 CTL responses in patients vaccinated with a recombinant virus encoding the antigen and also in patients vaccinated with peptide-pulsed dendritic cells. In contrast, for patients showing tumor regression after vaccination with peptide alone, CTL responses were almost never observed. It is possible that even those CTL responses that are below our present detection level can trigger a sequence of events that leads to tumor regression.
机译：癌症生殖细胞基因MAGE-3编码T淋巴细胞在许多肿瘤上识别的肿瘤特异性抗原。 HLA-A1呈递的MAGE-3抗原已用于转移性黑色素瘤患者的多项疫苗接种试验中。只有一小部分患者显示出肿瘤消退的证据。这些反应的低水平阻碍了将肿瘤排斥与针对疫苗的细胞毒性T淋巴细胞（CTL）反应相关联的尝试。在非癌性个体中，针对抗原MAGE-3.A1的T细胞前体的频率为≈4x 10〜（-7）CD8 T细胞。在一个人中分析了这些抗MAGE-3.A1前体的T细胞受体库的多样性。结果表明该库很可能包含> 100个克隆型。在此基础上，不仅可以利用血液中CTL前体的频率，还可以利用显性克隆型的存在来确定患者中抗MAGE-3.A1反应的存在低至10〜（-6）。 CD8。通过这种方法，我们在接种了编码抗原的重组病毒的患者以及接种了肽脉冲树突状细胞的患者中观察到了肿瘤消退与抗MAGE-3.A1 CTL反应之间的相关性。相反，对于仅用肽接种后显示肿瘤消退的患者，几乎从未观察到CTL反应。即使那些低于我们目前检测水平的CTL反应也可能触发一系列导致肿瘤消退的事件。

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