Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC) class I expression by increasing interferon-gamma (IFN-gamma)

Tumor immunity is primarily mediated by cells as CD8(+) cytotoxic T lymphoc ytes (CTL) recognize tumor antigen by MHC class I molecules. But most tumor s are associated with a decreased expression of MHC class I to escape the a ntitumor immunity of the host. Our previous data have demonstrated that MPL has an antitumor effect on metastatic lung cancer of Bib melanoma with enh ancing cytotoxicity due to increase of IFN-gamma and IL-2, and decrease of IL-4, which indicates the stimulation of type 1 helper T cells (Th1). To de termine the effects of MPL, IFN-gamma , TNF-alpha, and IL-1 alpha on MHC cl ass I expression of B16 melanoma cells, we evaluated the expression of MHC class I molecules with treatments of MPL, IFN-gamma, TNF-alpha, and IL-1 al pha by Row cytometry,The supernatant of MPL-treated spleen cells in vitro u pregulated the expression of MHC class I molecules of B16 melanoma cells co mpared to the control supernatant of spleen cells. The MHC class I expressi on of B16 melanoma cells treated with IFN-gamma, but not TNF-alpha or IL-1 alpha, increased in a time-dependent manner. In conclusion, MPL upregulated MHC class I expression of B16 melanoma cells by activating spleen sells vi a IFN-gamma. These data suggest that increased IFN-gamma by MPL is responsi ble for the upregulation of MHC class I expression to augment cytotoxicity. Therefore, we suggest that MPL could play an important role in immunothera py.