Geranylgeranyl transferase inhibition stimulates anti-melanoma immune response through MHC Class I and costimulatory molecule expression.

SPECIFIC AIMSDeficiencies in membrane expression of tumor-derived peptide/MHC Class I complexes are often correlated with tumor progression. The primary aim of this work was to examine the effects of statins on IFN-γ-induced expression of MHC Class I in melanoma cell membranes. The latter aim was to test statin capacity to favor immunogenicity due to overexpression of molecules implicated in the setting of anti-tumor response (namely MHC Class I and costimulatory molecules expression) and finally to identify the check-point activity of statins for these effects on the mevalonate pathway.PRINCIPAL FINDINGS1. Statins and geranylgeranyl transferase I inhibitor (GGTI-298), but not farnesyl transferase inhibitor (FTI-277), enhance MHC Class I expression induced by mIFN-γMurine B16F10 melanoma cell line, which has deficient MHC Class I (H-2 Class I) antigen surface expression that can be corrected by mIFN-γ administration, was chosen for this study. The expression of H-2Kb molecules was analyzed by cytofluorome...