CD226 and acute myeloid leukemia: Further, the total absence of NKG2D ligands on AML leukemic stem cells [110], the release of a soluble NKG2D ligand resulting in downregulation of the corresponding receptor on NK-cells [111], reduced expression of activating receptors on NK-cells such as DNAM-1 (CD226) [112] and the induction of co-inhibitory receptors on NK-cells such as TIGIT [59], lead to impaired NK-cell activity.