title: Immunoglobulin GM and FcγRIIIa genotypes influence cytotoxicity of neuroblastoma cells.
abstract: Immunoglobulin GM (γ marker) allotypes are strongly associated with neuroblastoma, but the mechanism is not known. One mechanism could involve antibody-dependent cell-mediated cytotoxicity (ADCC) of neuroblastoma cells. Using an ADCC inhibition assay, we show that IgG1 expressing GM 3+,1-,2- allotypes blocked all phenylalanine-expressing FcγRIIIa present on NK cells, resulting in total inhibition of anti-GD2 antibody-mediated ADCC of GD2-overexpressing neuroblastoma cells. In contrast, the inhibitory effect of this protein was significantly lower when the NK cells were homozygous for the valine allele of FcγRIIIa (100 vs. 21%; p=0.00004). These and other findings presented here could lead to a more effective immunotherapy of neuroblastoma.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: pandeyj@musc.edu.
authors.forename: Janardan P
authors.initials: JP
authors.lastname: Pandey
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Aryan M
authors.initials: AM
authors.lastname: Namboodiri
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005838:Genotype; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C496124:FCGR3A protein, human; D007129:Immunoglobulin Gm Allotypes; D017452:Receptors, IgG
keywords: ADCC; Anti-GD2 antibodies; FcγR genotypes; GM allotypes; Neuroblastoma