Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis.
In this study, in an attempt to identify neuroblastoma-associated surface antigens, we generated mAbs against the ACN neuroblastoma cell line. A mAb was selected (5B14) that reacted with all neuroblastoma cell lines analyzed and allowed detection of tumor cell infiltrates in bone marrow aspirates from neuroblastoma patients. In cytofluorimetric analysis, unlike anti-disialoganglioside mAb, 5B14 mAb did not display reactivity with normal bone marrow hematopoietic cell precursors, thus representing a highly specific marker for identifying neuroblastoma cells. Molecular analysis revealed that the 5B14 mAb-reactive surface glycoprotein corresponded to the recently identified 4Ig-B7-H3 molecule. Remarkably, mAb-mediated masking of the 4Ig-B7-H3 molecule on cell transfectants or on freshly isolated neuroblastoma cells resulted in enhancement of natural killer-mediated lysis of these target cells. These data suggest that 4Ig-B7-H3 molecules expressed at the tumor cell surface can exert a protective role from natural killer-mediated lysis by interacting with a still undefined inhibitory receptor expressed on natural killer cells.
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Via L. B. Alberti 2, 16132 Genoa, Italy.
Roberta
R
Castriconi
Alessandra
A
Dondero
Raffaella
R
Augugliaro
Claudia
C
Cantoni
Barbara
B
Carnemolla
Angela Rita
AR
Sementa
Francesca
F
Negri
Romana
R
Conte
Maria Valeria
MV
Corrias
Lorenzo
L
Moretta
Alessandro
A
Moretta
Cristina
C
Bottino
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000378:metabolism*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D060887:B7 Antigens; D018122:B7-1 Antigen; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; C486038:Cd276 protein, mouse; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D007371:Interferon-gamma