The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy.
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans. Preliminary results with IDO inhibitors, usually combined with other anti-cancer drugs, seem encouraging. Further studies are needed to clarify the conditions in which IDO inhibitors can be of value as an anti-cancer strategy. In addition, further research should address whether the expression of IDO in tissue or blood can be a marker to select patients who can benefit most from IDO inhibition.
Department of Dermatology, Ghent University Hospital, Belgium; Dermatology Research Unit, Ghent, Belgium; Immuno-Oncology Network Ghent (ION Ghent), Belgium; Cancer Research Institute Ghent (CRIG), Belgium. Electronic address: lieve.brochez@UGent.be.
Lieve
L
Brochez
Department of Dermatology, Ghent University Hospital, Belgium; Dermatology Research Unit, Ghent, Belgium; Immuno-Oncology Network Ghent (ION Ghent), Belgium.
Ines
I
Chevolet
Department of Medical Oncology, Ghent University Hospital, Belgium; Immuno-Oncology Network Ghent (ION Ghent), Belgium.
Vibeke
V
Kruse
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D010091:Oximes / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010091:Oximes; D013449:Sulfonamides; C000613752:epacadostat; D014364:Tryptophan; C525396:1-methyltryptophan
Cancer; Epacadostat; IDO inhibition; Immune tolerance; Indoleamine 2-3-dioxygenase (IDO); Indoximod; Melanoma