Fig. 1
From: Targeting the indoleamine 2,3-dioxygenase pathway in cancer
Mechanisms of IDO pathway activity in immune tolerance. The enzyme IDO catalyzes the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. Accordingly, IDO can provoke tryptophan shortage, which results in mTORC1 inhibition and GCN2 activation, in turn leading to anergy of effector T cells. Tryptophan’s degradation leads to production of bioactive kynurenine pathway compounds, which activate the AHR, resulting in promotion of Treg differentiation. TC, tumor cell; DC, dendritic cell; MФ, macrophage; EC, endothelial cell; FB, fibroblast; IDO, indoleamine-2,3-dioxygenase 1; Trp, tryptophan; Krn, kynurenine; mTORC1, mechanistic target of rapamycin (serine/threonine kinase) complex 1; GCN2, general control nondepressible-2; AHR, aryl hydrocarbon receptor; Treg, regulatory T cell