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 lymphocytes (CTL) recognize tumor antigen by MHC class I molecules. But most tumors are associated with a decreased expression of MHC class I to escape the antitumor immunity of the host. Our previous data have demonstrated that MPL has an antitumor effect on metastatic lung cancer of B16 melanoma with enhancing 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 determine the effects of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha on MHC class 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 alpha by flow cytometry. The supernatant of MPL-treated spleen cells in vitro upregulated the expression of MHC class I molecules of B16 melanoma cells compared to the control supernatant of spleen cells. The MHC class I expression 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 cells via IFN-gamma. These data suggest that increased IFN-gamma by MPL is responsible for the upregulation of MHC class I expression to augment cytotoxicity. Therefore, we suggest that MPL could play an important role in immunotherapy.
Cho
C H
CH
Department of Internal Medicine, College of Medicine, Inha University, Seoul, Korea.
Lee
B K
BK
Kwak
S M
SM
Kim
J D
JD
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D008050:Lipid A; D007371:Interferon-gamma; C048436:monophosphoryl lipid A