Figure 1

IDO, PGE2 and HLA-E: a core set of immunosuppressants and immunomodulators acting on both T and NK cells. Tumor cells create a potentially inhibitory microenvironment by producing IDO (causing tryptophan depletion and L-kynurenine accumulation), secreting PGE2, and expressing surface HLA-E. IDO and PGE2 inhibit T cell functions both directly and indirectly (through Treg cells), and down-regulate NK receptors, although with a different spectrum of activity. HLA-E binds the inhibitory receptor NKG2A, although it may also bind the activating receptor NKG2C. In addition, PGE2 is known to suppress IFN-γ production by T and NK cells, IL12/IL15 responsiveness of NK cells, and both production of, and responsiveness to, IL2 by T cells[1, 8–10, 15].