2. Academic Validation
  3. Inflammatory Reprogramming with IDO1 Inhibitors: Turning Immunologically Unresponsive 'Cold' Tumors 'Hot'

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.
George C Prendergast 1,  Arpita Mondal 2,  Souvik Dey 2,  Lisa D Laury-Kleintop 2,  Alexander J Muller 3
Affiliations

Affiliations

  • 1 Lankenau Institute for Medical Research (LIMR), Wynnewood, PA, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: [email protected].
  • 2 Lankenau Institute for Medical Research (LIMR), Wynnewood, PA, USA.
  • 3 Lankenau Institute for Medical Research (LIMR), Wynnewood, PA, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
PMID: 29413421 DOI: 10.1016/j.trecan.2017.11.005
Abstract

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.

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