Using therapeutic viruses to understand the action of human natural killer cells

Abstract: Natural killer (NK) cells have an innate ability to detect and kill virus-infected cells and tumour cells. These functions place them central stage in the action of oncolytic viruses (OV), viruses that are used to treat human cancer. Evidence suggests that NK cells are important for the action of OV in animal models but the mechanisms by which OV activate NK cells and the consequences of such activity are not well understood. I will introduce NK cells and OV and describe our research in which we use OV in the lab and in clinical trials in cancer patients to dissect the mechanisms of NK cell activation by viruses. Not surprisingly, type I interferon plays a major role in regulating NK cell activation following exposure to OV, this includes the regulation of NK cell cytotoxicity, proliferation and activity that shapes the adaptive immune response. These studies of OV have important implications for their use in cancer treatment but also provide a model for how human NK cells respond to viral infection.