Blocking aryl hydrocarbon receptor remodels myeloid-T cell crosstalk and enhances anti-PD-1 response in the tumor microenvironment

Purpose

Cancer metabolism-associated immune suppression remains a major barrier to durable therapeutic responses. Indoleamine-2,3-dioxygenase 1 has been pursued as a therapeutic target, but incomplete pathway suppression has limited clinical success. As the aryl hydrocarbon receptor is a ligand-activated transcription factor and downstream effector of tryptophan metabolism, we investigated how myeloid-cell aryl hydrocarbon receptor signaling shapes the tumor immune microenvironment and whether its inhibition can restore antitumor immunity.