Natural killer (NK) cells express many newly identified activating and inhibitory receptors that upon engagement by cognate ligands on target tumor cells regulate NK cell antitumor activity. Recently, several paired NK cell receptor families that include receptors with similar binding specificities but opposite function have been defined. The expression of most important activating receptors, natural killer group 2D (NKG2D), natural cytotoxic receptors (NCR), DNAX accessory molecule-1 (DNAM1) and activating killer cell immunoglobulin-like receptors (KAR) is often decreased, while the expression of most prominent inhibitory NK cell receptors, killer cell inhibitory immunoglobulin-like receptors (KIR) and CD94/NKG2A, may occasionally be increased in malignancies. These data indicate that impaired NK cell antitumor response results from NK cell receptor alterations induced by suppressive factors in the tumor microenvironment, including cytokines, growth factors, enzymes and metabolites, as well as by chronic NK cell receptor engagement by the tumor. The established alterations in NK cell receptor expression in cancer patients represent potential disease biomarkers and may aid in choosing therapies that upregulate activating or block inhibitory receptor function. Accumulating knowledge of NK cell biology has been helpful in creating novel therapeutic approaches that by release from tumor-influenced immunosuppression potentiate NK cell activity in cancer patients.
Part of the book: Natural Killer Cells