IDO1 and glioblastoma: Under physiological conditions, IDO1 modulates immune tolerance by regulating T cell function.327 In GBM, IDO1 expression is significantly elevated.328 Elevated IDO1 activity in GBM leads to tryptophan depletion and increased kynurenine production, which leads to GCN activation, PD-1/PD-L1 upregulation, AHR activation, and increased kynurenine metabolite production.329 This leads to the inhibition of effector T cell and NK cell functions while promoting Treg differentiation, thus impairing antitumor immunity330 (Fig. 6).