Interferon-mediated in vivo induction of β₂-microglobulin on small-cell lung cancers and mid-gut carcinoids

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and β₂-microglobulin, β₂m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced β₂m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining β₂m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-α therapy. Before IFN treatment, 3 4 SCLC tumors and 5 7 mid-gut carcinoids did not express β₂m. By contrast, all tumors showed considerable expression of β₂m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.