Doyle A, Martin W J, Funa K, Gazdar A, Carney D, Martin S E, Linnoila I, Cuttitta F, Mulshine J, Bunn P
J Exp Med. 1985 May 1;161(5):1135-51. doi: 10.1084/jem.161.5.1135.
We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.
我们发现，在人小细胞肺癌（SCLC）细胞系和新鲜肿瘤样本中，I类主要组织相容性抗原HLA - A、B、C以及β2微球蛋白（β2m）的表达明显不足。通过放射结合试验和间接免疫荧光试验均证实了HLA - A、B、C以及β2微球蛋白（β2m）抗原表达的缺陷。用针对I类抗原的抗体对代谢标记细胞进行免疫沉淀显示，大多数SCLC细胞系几乎没有合成β2m和HLA - A、B、C蛋白。使用人HLA - A、B和β2m cDNA探针进行的Northern印迹分析表明，几乎所有检测的SCLC细胞系中HLA和β2m mRNA的量都显著减少，但用干扰素处理SCLC细胞系可诱导这两种基因产物的产生。我们得出结论，与其他类型的肺癌相比，人SCLC的特征在于HLA - A、B、C和β2m基因的转录大幅减少，这表明存在一种逃避宿主对肿瘤免疫反应的机制，并且在这种类型的肿瘤细胞中存在一种类似E1a的产物。
