title: Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L.
abstract: Tumour cells display low to absent expression of costimulatory molecules. Here, we have investigated the expression of costimulatory molecules (CD40, CD80, CD86, PD-1L, B7H2, OX40L and 4-1BBL) in human neuroblastoma (NB) cells, since virtually no information is available on this issue. Both established NB cell lines and primary tumours were tested by RT-PCR and flow cytometry. Neuroblastoma cell lines expressed the transcripts of all costimulatory molecule genes, but not the corresponding proteins. Culture of NB cell lines with human recombinant (r)IFN-gamma induced surface expression of CD40 in half of them. Primary NB cells showed CD40, CD80, CD86, OX40L, 4-1BBL, but not PD-1L and B7H2, mRNA expression. Surface CD40 was consistently detected on primary NB cells by flow cytometry. Interferon-gamma gene-transfected NB cells expressed constitutively surface CD40 and were induced into apoptosis by incubation with rCD40L through a caspase-8-dependent mechanism. CD40 may represent a novel therapeutic target in NB.
authors.affiliation: Laboratory of Oncology, G Gaslini Institute, Largo G Gaslini, 5, 16148 Genova, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Airoldi
authors.forename: S
authors.initials: S
authors.lastname: Lualdi
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.forename: L
authors.initials: L
authors.lastname: Raffaghello
authors.forename: M
authors.initials: M
authors.lastname: Occhino
authors.forename: C
authors.initials: C
authors.lastname: Gambini
authors.forename: V
authors.initials: V
authors.lastname: Pistoia
authors.forename: M V
authors.initials: MV
authors.lastname: Corrias
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D017209:Apoptosis; D019013:CD40 Antigens / Q000032:analysis / Q000276:immunology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009447:Neuroblastoma / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000943:Antigens, Differentiation; D019013:CD40 Antigens; D007371:Interferon-gamma; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases