IDO1

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step of tryptophan catabolism into kynurenine, modulating immune tolerance by depleting local tryptophan and suppressing effector T-cell proliferation^[1][2]. Mechanistically, IDO1 activity triggers immunosuppressive signaling via activation of regulatory T cells and myeloid-derived suppressor cells, contributing to tumor immune evasion^[3][4][5]. IDO1 interacts with the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) pathway, promoting T-cell suppression and facilitating tumor growth across multiple cancer types, including colorectal, pancreatic, and breast cancers^[6][7][8][9]. Compared with its related isoforms IDO2 and TDO2, IDO1 predominantly mediates local immunosuppression, whereas IDO2 is associated with B cell-driven inflammation and TDO2 maintains systemic tryptophan homeostasis^[10][11]. In disease models, IDO1 inhibition enhances anti-tumor immune responses, sensitizes tumors to radiotherapy, and modulates the tumor microenvironment toward a T cell-inflamed phenotype^[12][8][9]. Selective inhibitors such as epacadostat and downstream modulators including indoximod exhibit dual roles in blocking IDO1 enzymatic activity and engaging mTORC1 or AhR signaling, providing tools for experimental cancer immunotherapy^[6][13]. Despite mixed clinical outcomes, IDO1-targeted interventions remain relevant for research on immunometabolic modulation and combination strategies with checkpoint blockade^[4][7][14].