IDO1 and neoplasm: Mechanistically, PGE2 produced by HCC cells has been shown to cooperate with products of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) at inducing the downregulation of NKG2D and other NK cell-activating receptors (Box 1) in tumor-infiltrating human NK cells, resulting in profound dysfunction [131].