Natural killer cells and cancer.

Natural killer (NK) cells are lymphocytes that were first identified for their ability to kill tumor cells without deliberate immunization or activation. Subsequently, they were also found to be able to kill cells that are infected with certain viruses and to attack preferentially cells that lack expression of major histocompatibility complex (MHC) class I antigens. The recent discovery of novel NK receptors and their ligands has uncovered the molecular mechanisms that regulate NK activation and function. Several activating NK cell receptors and costimulatory molecules have been identified that permit these cells to recognize tumors and virus-infected cells. These are modulated by inhibitory receptors that sense the levels of MHC class I on prospective target cells to prevent unwanted destruction of healthy tissues. In vitro and in vivo, their cytotoxic ability can be enhanced by cytokines, such as interleukin (IL)-2, IL-12, IL-15 and interferon alpha/beta (IFN-alpha/beta). In animal studies, they have been shown to play a critical role in the control of tumor growth and metastasis and to provide innate immunity against infection with certain viruses. Following activation, NK cells release cytokines and chemokines that induce inflammatory responses; modulate monocyte, dendritic cells, and granulocyte growth and differentiation; and influence subsequent adaptive immune responses. The underlining mechanism of discriminating tumor cells and normal cells by NK cells has provided new insights into tumor immunosurveillance and has suggested new strategies for the treatment of human cancer.