HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination
HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination
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DOI：
10.1007/s00262-006-0226-7
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Garrido, Federico
中科院分区：
文献类型：
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作者：
Cabrera, Teresa;Lara, Ester;Garrido, Federico
我们对肿瘤特异性免疫反应和肿瘤逃逸机制的了解已大大增加。 HLA I 类抗原缺陷仍然是重要的肿瘤逃逸机制，因为它们在恶性疾病过程中影响肿瘤细胞与特定 T 和 NK 细胞之间的相互作用。我们在这里研究了从用自体黑色素瘤细胞疫苗（M-VAX）免疫的黑色素瘤患者获得的六个皮下转移瘤中的 HLA I 类表达。我们在本文中报道，这些转移性病灶上的 HLA I 类抗原表达与疾病的病程密切相关。切除时部分消退的三个转移瘤显示出强烈的 HLA I 类表达，而进展的转移瘤则显示出非常弱的染色或使用大多数抗 HLA I 类单克隆抗体的阴性染色。对从显微解剖的肿瘤组织中获得的样本进行实时定量PCR显示，两种类型的转移瘤之间的HLA-ABC重链和β2m mRNA水平存在显着差异，即进展性转移瘤中水平较低，而消退性转移瘤中水平较高，这证实了免疫组织学结果。据我们所知，这是第一份报告，其中不同 HLA I 类阳性和阴性黑色素瘤转移的临床结果可以分别与疾病的消退和进展明确相关。
Our knowledge of the mechanisms underlying tumor-specific immune response and tumor escape has considerably increased. HLA class I antigen defects remain an important tumor escape mechanism since they influence the interactions between tumor cells and specific T and NK cells in the course of malignant disease. We have studied here HLA class I expression in six subcutaneous metastases obtained from a melanoma patient immunized with an autologous melanoma cell vaccine (M-VAX). We report in this paper that HLA class I antigen expression on these metastatic lesions strongly correlated with the course of the disease. The three metastases that were partially regressing at the time of their excision showed a strong HLA class I expression, whereas the progressing ones showed a very weak or negative staining with most of the anti-HLA class I mAbs used. Real-time quantitative PCR of the samples obtained from microdissected tumor tissue revealed a significant difference in the mRNA levels of HLA-ABC heavy chain and beta 2m between the two types of metastases, i.e., lower levels in progressing metastases and high levels in regressing ones, confirming the immunohistological findings. This is, to our knowledge, the first report where the clinical outcome of different HLA class I positive and negative melanoma metastases can be clearly correlated with the regression and progression of the disease, respectively.