Inflammatory Reprogramming with IDO1 Inhibitors: Turning Immunologically Unresponsive 'Cold' Tumors 'Hot'

Trends Cancer. 2018 Jan;4(1):38-58. doi: 10.1016/j.trecan.2017.11.005. Epub 2017 Dec 21.


We discuss how small-molecule inhibitors of the tryptophan (Trp) catabolic enzyme indoleamine 2,3-dioxygenase (IDO) represent a vanguard of new immunometabolic adjuvants to safely enhance the efficacy of cancer immunotherapy, radiotherapy, or 'immunogenic' chemotherapy by leveraging responses to tumor neoantigens. IDO inhibitors re-program inflammatory processes to help clear tumors by blunting tumor neovascularization and restoring immunosurveillance. Studies of regulatory and effector pathways illuminate IDO as an inflammatory modifier. Recent work suggests that coordinate targeting of the Trp catabolic enzymes tryptophan 2,3-dioxygenase (TDO) and IDO2 may also safely broaden efficacy. Understanding IDO inhibitors as adjuvants to turn immunologically 'cold' tumors 'hot' can seed new concepts in how to improve the efficacy of cancer therapy while limiting collateral damage.

Keywords: immunometabolism; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cellular Reprogramming / genetics*
  • Cellular Reprogramming / immunology
  • Humans
  • Immunotherapy*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Inflammation / immunology
  • Inflammation / pathology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Small Molecule Libraries / therapeutic use
  • Tryptophan / metabolism
  • Tryptophan Oxygenase / antagonists & inhibitors
  • Tryptophan Oxygenase / immunology


  • IDO1 protein, human
  • IDO2 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Small Molecule Libraries
  • Tryptophan
  • Tryptophan Oxygenase