Effects of cytokines combined with high-dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule-1 in human ovarian cancers

Abstract

Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-I, class-II and ICAM-1 surface antigens before and after exposure to γ-irradiation and/or the cytokines TNF-α plus IFN-γ. All 7 fresh tumors expressed high levels of MHC class-I and ICAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-α plus IFN-γ. Similarly, class-II antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-α plus IFN-γ. Exposure to high doses of γ-irradiation also increased the expression of MHC class-I and ICAM-1 antigens, albeit to a modest degree. MHC class-I and ICAM-1 antigen expression was much lower on continuous human ovarian cell lines than on the fresh tumors. Exposure of these cells to TNF-α plus IFN-γ markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors. With the established ovarian cell lines, removal of cytokines caused a rapid down-regulation of antigen expression to basal levels within 6 days, while in the fresh tumors a low level of upregulation was still present at this time. In contrast, exposure to cytokines followed by high-dose γ-irradiation resulted in a highly significant and long-lasting expression of each surface antigen which was either up-regulated or induced by the cytokines. These data indicate that the combination of these modalities may be beneficial in generating optimal antigen expression for use of tumor cells in vaccine studies.