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 during the process of target cell lysis have been at least in part identified. These are members of a novel family of receptors that has been termed natural cytotoxicity receptors (NCR). The first three members of this emerging group of receptors are the NKp46, NKp44 and NKp30 molecules that all belong to the immunoglobulin superfamily. Blocking of these receptors inhibits NK-mediated cytotoxicity against a wide variety of tumor target cells. In the present study, we show that these NCR are also involved in NK-mediated killing of tumor cells of neural origin. Glioblastoma and neuroblastoma target cells were efficiently killed by all NK clones analyzed since little protection from NK lysis was mediated by HLA class I molecules. Blocking of one or another NCR inhibited cytotoxicity; however, optimal inhibition was only observed when the three receptors were blocked simultaneously. A sharp difference in cytotoxicity against neural tumors was demonstrated between NCR(bright) and NCR(dull) NK clones, further supporting the notion that NCR play a critical role in the induction of cytotoxicity against tumor target cells of different histotype. Finally, our data also indicate that CD16 does not function 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 NCR(bright)/NCR(dull) phenotype and CD16 expression.
Sivori
S
S
Dipartimento di Medicina Sperimentale (DIMES), Sezione di Istologia, Università di Genova, Via Marsano 10, 16132, Genova, Italy.
Parolini
S
S
Marcenaro
E
E
Castriconi
R
R
Pende
D
D
Millo
R
R
Moretta
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology; D001932:Brain Neoplasms / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis; D002860:Chromium Radioisotopes; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D009447:Neuroblastoma / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019002:CD56 Antigen; D002860:Chromium Radioisotopes; C112260:NCR1 protein, human; C112837:NCR2 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D017452:Receptors, IgG; D011971:Receptors, Immunologic