Furthermore, tumors and other cells present in the TME (dendritic cells, macrophages or endothelial cells) increase expression of the indoleamine-2,3-dioxygenase (IDO) – an immunosuppressive enzyme that cause a decrease in tryptophan amino acid concentration in extracellular environment (essentially required for the T cell function), induce the tumor-specific T cells exhaustion, and promote activation of Treg populations (67). Here, IDO1 is linked to neoplasm.