Fig. 3

Regulation, function, and targeting of IDO1 in cancer. a The upstream regulators of IDO1. IDO1 is expressed in cancer cells, endothelial cells, antigen-presenting cells, and stromal cells. IDO1 expression is regulated by IFNs, PD-1, oncogene activation (KIT or RAS), PAMPs, and DAMPs through relevant signaling pathways like IFN-γ/JAK/STAT, PI3K/PKC, and NF-κB. b The downstream effectors of IDO1 and IDO1 targeting. Three effector pathways (mTOR, GCN2, and AhR) mediate the effects of IDO1 activities in various types of cells in regard to immunosuppression, neovascularization, interactions with the gut microbiome, and the tumor microenvironment. Four strategies have been developed to target the IDO1 pathway in preclinical and clinical studies. IDO1, indoleamine 2, 3-dioxygenase 1; Trp, tryptophan; Kyn, kynurenine; IFN, interferon; PD-1, programmed death receptor 1; PAMP, pathogen-associated molecular pattern; DAMP, damage-associated molecular pattern; GCN2, general control over nonderepressible 2; mTOR, mammalian target of rapamycin; AhR, aryl hydrocarbon receptor; NK, natural killer cell; Treg, regulatory T cell; MDSC, myeloid-derived suppressor cell; EC, endothelial cell; DC, dendritic cell