Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: Critical role of DNAX accessory molecule-1-poliovirus receptor interaction

Roberta Castriconi, Alessandra Dondero, Maria Valeria Corrias, Edoardo Lanino, Daniela Pende, Lorenzo Moretta, Cristina Bottino, Alessandro Moretta

Research output: Contribution to journalArticle

Abstract

In the present study, we assessed the susceptibility of freshly isolated neuroblastoma cells to killing mediated by normal human natural killer (NK) cells and analyzed the receptor-ligand interactions that regulate this event. We show that killing of freshly isolated neuroblasts, similar to neuroblastoma cell lines, involves NKp46 and NKp30 (natural cytotoxicity receptors). However, freshly isolated neuroblasts were generally more resistant to NK-mediated lysis than conventional neuroblastoma cell lines. Moreover, a significant heterogeneity in susceptibility to lysis existed among neuroblastomas derived from different patients. Remarkably, susceptibility to lysis directly correlated with the surface expression, on neuroblasts, of poliovirus receptor [PVR (CD155)], a ligand for the DNAX accessory molecule-1 [DNAM-1 (CD226)] triggering receptor expressed by NK cells. Indeed, PVR-expressing neuroblastomas were efficiently killed by NK cells. Moreover, monoclonal antibody-mediated masking of either DNAM-1 (on NK cells) or PVR (on neuroblasts) resulted in strong inhibition of tumor cell lysis. Thus, assessment of the PVR surface levels may represent a novel useful criterion to predict the susceptibility/resistance of neuroblastomas to NK-mediated killing.

Original languageEnglish
Pages (from-to)9180-9184
Number of pages5
JournalCancer Research
Volume64
Issue number24
DOIs
Publication statusPublished - Dec 15 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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