Tumor cells, MDSCs, TAMs, and cancer associated fibroblasts (CAFs) actively deplete tryptophan through upregulation of indoleamine 2,3-dioxygenase (IDO), which its metabolite kynurenine has been shown to upregulate PD1 expression on CD8+ T cells (84, 85). The gene discussed is CD8A; the disease is neoplasm.