Natural killer (NK) cell receptors regulate the capacity of NK cells and in some cases T cells to attack tumor cells and infected cells. Cancer cells become susceptible to NK cells by up-regulating stimulatory ligands, such as the Raet1/Mult1/H60/ULBP/MICA families of proteins recognized by the NKG2D receptor. This presentation will discuss the role of activating receptors such as NKG2D in tumor surveillance in vivo and the molecular mechanisms and signaling pathways responsible for induction of NKG2D ligands in cancer cells and their relationship to major pathways regulating tumorigenesis. Evidence will be presented that tumor associated stress pathways induce NKG2D ligands by acting at distinct levels of biogenesis (transcription, mRNA stabilization, protein stabilization). The role of NKG2D recognition in mobilizing lymphocytes against tumors in vivo will be discussed.

Supported by grants from NCI, NIAID and Prostate Cancer Foundation.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN08-03.