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 beta2m 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.

译文

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会影响肿瘤细胞与特异性T和NK细胞之间的相互作用。我们在这里研究了用自体黑素瘤细胞疫苗 (m-vax) 免疫的黑素瘤患者获得的六个皮下转移中的HLA I类表达。我们在本文中报告了这些转移性病变上的HLA I类抗原表达与疾病的进程密切相关。切除时部分消退的三个转移灶显示出较强的HLA I类表达,而大多数使用的抗HLA I类mab,进展的转移灶显示出非常弱或阴性的染色。从显微解剖的肿瘤组织获得的样品的实时定量PCR显示,两种转移类型之间hla-abc重链和beta2m的mRNA水平存在显着差异,即进展转移中的水平较低,而消退中的水平较高,证实了免疫组织学发现。据我们所知,这是第一份报告,其中不同的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。

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