Role of TNF family ligands in antitumor activity of natural killer cells.
NK cells have the ability to destroy tumor cells by two main cytotoxic pathways, the well-known perforin/granzyme-mediated secretory/necrotic killing and the newly defined TNF family ligand-mediated apoptotic killing. The former mechanism is operative mainly against a few cultured leukemia cell targets, while the latter mediates substantial activity against most tumor cell targets. It also appears from emerging data that the apoptotic mechanism is the main antitumor pathway in vito. This review is focused on the apoptotic mechanism of killing, the molecules and cell signaling pathways involved in this process, and its potential biologic significance along with its relation to the secretory/necrotic cytolytic pathway.
Vujanovic
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Department of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, PA 15213, USA. vujanovicnl@msx.upmc.edu
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D008024:Ligands; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human