Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L.
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.
Airoldi
I
I
Laboratory of Oncology, G Gaslini Institute, Largo G Gaslini, 5, 16148 Genova, Italy.
Lualdi
S
S
Bruno
S
S
Raffaghello
L
L
Occhino
M
M
Gambini
C
C
Pistoia
V
V
Corrias
M V
MV
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
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