Tumor necrosis factor enhances HLA-A,B,C and HLA-DR gene expression in human tumor cells

Abstract

Tumor necrosis factor-alpha (TNF-alpha) exerts multiple biologic activities, which include such diverse effects as direct tumoricidal activity and stimulation of metabolic activities as well as expression of cell surface antigens on nonmalignant cells. We report here that in various human tumor cells TNF-alpha upregulates constitutively expressed HLA genes. Further, in a priori HLA-negative tumor cells, TNF-alpha enhances IFN-gamma-induced class I and class II HLA gene expression. In vitro transcription, Northern blot, and immunofluorescence analysis performed with the leukemic cell line K 562 reveal that TNF-alpha reversibly enhances IFN-gamma-induced HLA gene expression at the level of mRNA transcription. In addition, a posttranscriptional regulation of HLA gene expression by TNF-alpha is suggested from enhancement of HLA class I membrane expression in Colo 205 cells without measurable changes in steady state mRNA levels. Therefore, it is conceivable that TNF-alpha, similar to IFN-gamma, might provoke tumor rejection not only via direct tumoricidal action but also via enhancement of HLA antigens and induction of tumor-specific immune responses.