James B. DuHadaway

TL;DR: It is shown that IDO is under genetic control of Bin1, which is attenuated in many human malignancies, and that small-molecule inhibitors of IDO cooperate with cytotoxic agents to elicit regression of established tumors refractory to single-agent therapy.

TL;DR: Evidence is provided that the D and L stereoisomers exhibit important cell type-specific variations in activity that support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-mediated immunosuppression and enhance antitumor immunity in the setting of combined chemo-immunotherapy regimens.

TL;DR: It was found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression, pointing to a role for AhR in contributing to host fitness.

TL;DR: The discovery of a novel IDO-related tryptophan catabolic enzyme termed IDO2 that is preferentially inhibited by D-1MT is reported, which has implications for understanding the evolution of tumoral immune tolerance and for interpreting preclinical and clinical responses to IDO inhibitors being developed to treat cancer, chronic infection, and other diseases.

TL;DR: Pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds that were first to be evaluated as IDO inhibitors in clinical trials.