Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is a cytosolic haem-containing enzyme involved in the degradation of tryptophan to kynurenine. Although initially thought to be solely implicated in the modulation of innate immune responses during infection, subsequent discoveries demonstrated IDO1 as a mechanism of acquired immune tolerance. In cancer, IDO1 expression/activity has been observed in tumor cells as well as in the tumor-surrounding stroma, which is composed of endothelial cells, immune cells, fibroblasts, and mesenchymal cells. IDO1 expression/activity has also been reported in the peripheral blood. This manuscript reviews available data on IDO1 expression, mechanisms of its induction, and its function in cancer for each of these compartments. In-depth study of the biological function of IDO1 according to the expressing (tumor) cell can help to understand if and when IDO1 inhibition can play a role in cancer therapy.
Highlights
Indoleamine 2, 3-dioxygenase 1 (IDO1, hereafter referred to as IDO) is a 403 amino acid cytosolic haem-containing enzyme involved in the first, rate-limiting step of the tryptophan (Trp) metabolism to kynurenine (Kyn) [1, 2]
This study investigated in vivo IDO expression in multiple malignancies and normal cells in the stroma were observed to be IDO-negative in contrast to the tumor cells
Non-T-cell inflamed melanomas lacked these factors, suggesting that immune suppression might not be a property of tumor cells but rather an immune-intrinsic negative feedback process that follows the infiltration of activated CD8+ T-cells
Summary
Indoleamine 2, 3-dioxygenase 1 (IDO1, hereafter referred to as IDO) is a 403 amino acid cytosolic haem-containing enzyme involved in the first, rate-limiting step of the tryptophan (Trp) metabolism to kynurenine (Kyn) [1, 2]. Trp is an essential amino acid for which both neuropsychological as well as immunological functions have been described. Despite their shared function in Trp degradation, the IDO2 isoform and tryptophan 2, 3-dioxygenase (TDO2) have distinct inducers and patterns of tissue expression [3, 4]. IDO expression has been reported in these different compartments, the exact mechanisms for its distinct expression patterns and their functions are far from completely understood. In view of the complex interplay between malignant cells and their microenvironment, understanding IDO activation and its particular function in the different compartments may be of the outmost importance.
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