Indoleamine 2,3-Dioxygenase, an Immunomodulatory Protein, Is Suppressed by (−)-Epigallocatechin-3-gallate via Blocking of γ-Interferon-Induced JAK-PKC-δ-STAT1 Signaling in Human Oral Cancer Cells

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 γ-interferon (IFN-γ) 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-γ. The study results demonstrate that EGCG can inhibit transloca...