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.