Inflammatory reprogramming with IDO1 inhibitors: turningimmunologically unresponsive ‘cold’ tumors‘hot’

摘要

We discuss how small molecule inhibitors of the tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDOi) 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 activation in cancer supports inflammatory processes that IDOi can re-program 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 TDO and IDO2 may also safely broaden efficacy. Understanding IDOi as adjuvants to turn immunologically 'cold' tumors 'hot' can seed new concepts in how to improve the efficacy of cancer therapy while limiting its collateral damage.