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[Cancer Research 64, 9180-9184, December 15, 2004]
© 2004 American Association for Cancer Research

Immunology

Natural Killer Cell-Mediated Killing of Freshly Isolated Neuroblastoma Cells

Critical Role of DNAX Accessory Molecule-1–Poliovirus Receptor Interaction

Roberta Castriconi1,2, Alessandra Dondero1, Maria Valeria Corrias2, Edoardo Lanino2, Daniela Pende3, Lorenzo Moretta1,2,4, Cristina Bottino2 and Alessandro Moretta1,4

1 Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genoa, Italy; 2 Istituto Giannina Gaslini, Genoa, Italy; 3 Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; and 4 Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genoa, Italy

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.




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Copyright © 2004 by the American Association for Cancer Research.