Purpose: B7-DC on tumor cells was demonstrated to promote tumor immunity; however, the precise mechanism responsible for the aberrant B7-DC expression remains unknown. Interferon gamma (IFN-γ) can induce B7-DC expression on macrophages and has been shown to regulate anti-tumor immunity by various mechanisms. This study was designed to investigate the relationship of IFN-γ and B7-DC on tumor cells and further explored the signal transduction pathways involved.
Methods: RT-PCR and flow cytometry were used for the analysis of B7-DC expression on various tumor cells. The phosphorylation of p38, ERK1/2, JNK, Akt, and JAK2 was determined by Western blot.
Results: IFN-γ markedly up-regulated B7-DC expression on various tumor cells and resulted in the phosphorylation of JAK2, JNK, ERK, p38, and Akt. Inhibition of ERK or JNK pathway significantly decreased IFN-c-induced B7-DC expression, whereas inhibition of phosphorylation of Akt, p38, and JAK2 had very little effect on IFN-γ-induced B7-DC expression.
Conclusions: Our findings demonstrate that the pretreatment of tumor cells with IFN-γ enhances B7-DC expression through ERK and JNK pathways.