MICA and MICB, as well as ULBP 1-6 expression is tightly restricted in healthy cells, only upregulated during stress and cellular transformation [1], and are recognised by the NKG2D receptor, which activates NK cells [2]. However, looking at just AML, expression can vary [3,4].
So going forward, I hope to see a number of different combinations tested. Bortezomib can increase the cell surface expression of NKG2D ligands, resulting in the increased killing by NK cells [5]. Histone deacetylase inhibitors have also been shown to increase expression of NKG2D ligands [6-8]. Treatment resulted in increased recognition and increased sensitivity to NK cell lysis [9]. In addition, all-trans retinoic acid or valproic acid in patients with AML induced NKG2D ligands on the surface of leukemic cells [10,11].
Finally, the use of a PARP1 inhibitor, could increase AML leukemic stem cell killing [12].