Immune escape is a characteristic of
cancer progression, but its underlying molecular mechanism is still poorly understood. An immunomodulatory
protein, indoleamide 2,3-dioxygenase (IDO), is induced by
gamma-interferon (IFN-gamma) in several immune cells; those cells are observed in
cancer cell microenvironment and can enhance immune escape. Previous studies show that IDO is expressed in the process of
tumor formation and associated with
cancer cell immune tolerance. By locally degrading
tryptophan, IDO inhibits the proliferation of T lymphocytes and induces T cell apoptosis, leading to suppression of T cell response. In this study, (-)-epigallocatechin-3-gallate (EGCG), the major constituent of
green tea, is found to significantly inhibit the expression of IDO in human
oral cancer cell lines. EGCG suppresses the induction of IDO at transcriptional level. Activation of STAT1 is discovered to play an important role in regulating IDO expression by IFN-gamma. The study results demonstrate that EGCG can inhibit translocation of STAT1 into nucleus in IFN-gamma-stimulated human
oral cancer cells. In addition, both
tyrosine and
serine phosphorylation of STAT1 are revealed to be suppressed by EGCG. Moreover, phosphorylation of PKC-delta, JAK-1, and JAK-2, which are the upstream event for the activation of STAT1, are also inhibited by EGCG in IFN-gamma-stimulated human
oral cancer cells. These data show that EGCG inhibited IDO expression by blocking the IFN-gamma-induced JAK-PKC-delta-STAT1 signaling pathway. This study indicates that EGCG is a potential
drug for immune and target
therapy to enhance
cancer therapy by increasing antitumor immunity.