Neoplastic cells as targets of spontaneously cytotoxic lymphocytes: studies with natural killer-like cell lines

Native natural killer (NK) cells comprise a heterogeneous family of lymphocytes distributed among several organs, which display spontaneous cytotoxic reactions directed against a broad range of tumor targets. In these studies, murine cell lines have been established in vitro following the selective expansion of bone marrow- and spleen-derived killer progenitors in culture medium supplemented with interleukin-2. Several clones of independent origin have been characterized in order to determine the extent of their phenotypic and functional diversity. With few exceptions most of them were found to be highly effective in lysing a variety of tumor cell lines, to share common cell surface alloantigens, lectin-binding receptors, and cytochemical markers. The presence of prominent azurophilic cytoplasmic granules is the most characteristic ultrastructural feature of these cells. In attempting to elucidate the nature of membrane components specifically recognized by NK cells we compared several isogenic tumor cell variants selected on the basis of their differential NK susceptibility, immunogenicity, metastatic potential or resistance to cytotoxic plant lectins. Sialylated glycoconjugates exposed on the external face of the tumor cell membrane appear to be essential determinants in the interaction between NK cells and their targets. Permanent cell lines retaining most of the functional attributes of endogenous NK cells may prove instrumental in understanding their role during tumor progression.