The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy

Eur J Cancer. 2017 May:76:167-182. doi: 10.1016/j.ejca.2017.01.011. Epub 2017 Mar 18.

Abstract

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.

Keywords: Cancer; Epacadostat; IDO inhibition; Immune tolerance; Indoleamine 2-3-dioxygenase (IDO); Indoximod; Melanoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis / immunology
  • Cell Proliferation
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Immune Tolerance / immunology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Oximes / therapeutic use
  • Sulfonamides / therapeutic use
  • T-Lymphocytes / immunology
  • Tryptophan / analogs & derivatives
  • Tryptophan / therapeutic use

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Oximes
  • Sulfonamides
  • epacadostat
  • Tryptophan
  • 1-methyltryptophan