Tumoral NKG2D alters cell cycle of acute myeloid leukemic cells and reduces NK cell-mediated immune surveillance

Abstract

Abstract The stimulatory natural killer group 2 member D (NKG2D) lymphocyte receptor, initially discovered and expressed mostly on natural killer (NK) cells, T cells and natural killer T cells, can promote tumor immune surveil- lance. However, with increasing tumor grade, tumors themselves express NKG2D to self-stimulate oncogenic pathways. To confirm that cancer cells themselves express NKG2D, we have now investigated the role of the tumoral NKG2D in NK cell-mediated immune surveillance. Both anti-NKG2D and shRNA to that down-regulated tumoral NKG2D increased the number of cells in G1 phase and S phase, increased the expression of cyclin E–CDK2 and decreased P21. In addition, CD107a, IFN-c and TNF-a increased when the cells were treated with anti-NKG2D which suggests that blocking tumoral NKG2D could aug- ment tumor surveillance of NK cells. Altogether, tumoral NKG2D stimulates cell propaga