Involvement of natural cytotoxicity receptors in human natural killer cell-mediated lysis of neuroblastoma and glioblastoma cell lines

The surface receptors involved in natural killer (NK) cell triggering durin g the process of target cell lysis have been at least in part identified. T hese are members of a novel family of receptors that has been termed natura l cytotoxicity receptors (NCR). The first three members of this emerging gr oup of receptors are the NKp46. NKp44 and NKp30 molecules that all belong t o the immunoglobulin superfamily. Blocking of these receptors inhibits NK-m ediated cytotoxicity against a wide variety of tumor target cells. In the p resent study, we show that these NCR are also involved in NK-mediated killi ng of tumor cells of neural origin. Glioblastoma and neuroblastoma target c ells were efficiently killed by all NK clones analyzed since little protect ion from NK lysis was mediated by HLA class I molecules. Blocking of one or another NCR inhibited cytotoxicity; however, optimal inhibition was only o bserved when the three receptors were blocked simultaneously. A sharp diffe rence in cytotoxicity against neural tumors was demonstrated between NCRbri ght and NCRdull NK clones, further supporting the notion that NCR play a cr itical role in the induction of cytotoxicity against tumor target cells of different histotype. Finally. our data also indicate that CD16 does not fun ction as a triggering receptor involved in lysis of neural tumors since no difference in cytotoxicity could be substantiated between CD16(+) and CD16( -) NK clones and no correlation could be detected between the NCRbright/NCR dull phenotype and CD16 expression. (C) 2000 Elsevier Science B.V. All righ ts reserved.