Unlicensed NK cells target neuroblastoma following anti-GD2 antibody treatment. Academic Article uri icon

Overview

abstract

  • Survival outcomes for patients with high-risk neuroblastoma (NB) have significantly improved with anti-disialoganglioside GD2 mAb therapy, which promotes NK cell activation through antibody-dependent cell-mediated cytotoxicity. NK cell activation requires an interaction between inhibitory killer cell immunoglobulin-like receptors (KIRs) and HLA class I ligands. NK cells lacking KIRs that are specific for self HLA are therefore "unlicensed" and hyporesponsive. mAb-treated NB patients lacking HLA class I ligands for their inhibitory KIRs have significantly higher survival rates, suggesting that NK cells expressing KIRs for non-self HLA are mediating tumor control in these individuals. We found that, in the presence of mAb, both licensed and unlicensed NK cells are highly activated in vitro. However, HLA class I expression on NB cell lines selectively inhibited licensed NK cell activity, permitting primarily unlicensed NK cells to mediate antibody-dependent cell-mediated cytotoxicity. These results indicate that unlicensed NK cells play a key antitumor role in patients undergoing mAb therapy via antibody-dependent cell-mediated cytotoxicity, thus explaining the potent "missing KIR ligand" benefit in patients with NB.

publication date

  • August 6, 2012

Research

keywords

  • Antibodies, Monoclonal
  • Antibody-Dependent Cell Cytotoxicity
  • Antineoplastic Agents
  • Gangliosides
  • Immunoglobulin G
  • Killer Cells, Natural
  • Neuroblastoma

Identity

PubMed Central ID

  • PMC3428088

Scopus Document Identifier

  • 84865960648

Digital Object Identifier (DOI)

  • 10.1093/intimm/7.3.393

PubMed ID

  • 22863621

Additional Document Info

volume

  • 122

issue

  • 9