This study showed the potential of resveratrol to inhibit the expression and activity of interferon-gamma (IFN-gamma)-induced indoleamine 2,3-dioxygenase (IDO) in bone marrow-derived dendritic cells (BMDCs). The mechanism of suppression was associated with the activity of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and protein kinase C delta (PKC delta). In addition, resveratrol-mediated IDO suppression in IFN-gamma-stimulated BMDCs appears to play a pivotal role in anti-tumor activity through the regulation of CD8(+) T cell polarization and cytotoxic T lymphocyte (CTL) activity. Systemic administration of resveratrol suppressed tumor growth in EG7 thymoma-bearing mice in an IDO-dependent manner. Taken together, resveratrol not only regulates immune response through the regulation of IDO in a JAK/STAT1- and PKC delta-dependent manner, but also modulates the IDO-mediated immune tolerance in EG7 thymoma. (C) 2012 Elsevier Inc. All rights reserved.