Use of Activated Natural Killer Cells for Tumor Immunotherapy in Mouse and Human

Natural killer (NK) cells are a subset of lymphocytes with a distinct morphologic appearance (large granular lymphocytes [LGLs]) and the ability to spontaneously kill virally infected or tumor targets but to spare most normal cells (1 ). These effector cells are now known to be able to eliminate tumor cells by mechanisms involving either necrosis or apoptosis or both (2 ), and upon activation to produce and secrete a broad spectrum of cytokines (1 ). NK cells respond to a variety of biologic agents, including cytokines such as interleukin-2 (IL-2), IL-12, or interferons, by upregulation of cytolytic, secretory, and/or proliferative functions (1 ). They represent from 5% to 15% of peripheral blood lymphocytes in humans and account for a substantial but variable proportion of tissue-resident lymphocytes. In rodents, NK cells are mainly found in the spleen, liver, and lung tissues as well as in the blood (1 ). Phenotypic characteristics of NK cells are variable, depending on the state of their activation, but surface expression of CD16 (FcγRIII), CD56 (in humans), NKR-P1 (in rats), or NK1.1 (in mice) and the absence of the T-cell receptor complex on the cell surface have been accepted as the markers defining these effector cells.