Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction.
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.
Castriconi
Roberta
R
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genoa, Italy.
Dondero
Alessandra
A
Corrias
Maria Valeria
MV
Lanino
Edoardo
E
Pende
Daniela
D
Moretta
Lorenzo
L
Bottino
Cristina
C
Moretta
Alessandro
A
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002648:Child; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D009447:Neuroblastoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011991:Receptors, Virus / Q000096:biosynthesis / Q000276:immunology*; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor