We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and β2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and β2-microglobulin (β2m) 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 β2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and β2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and β2m 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 β2m 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.
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