title: CD40 cross-linking enhances the immunogenicity of Burkitt's-lymphoma cell lines.
abstract: Epstein-Barr-virus (EBV)-positive Burkitt's-lymphoma (BL) cell lines are not recognized by EBV-specific T cells, due to their non-immunogenic phenotype and restricted expression of latent EBV genes. We tested whether triggering of CD40 can alter the phenotype of the tumor cells with regard to: (i) expression of surface markers, (ii) expression of viral antigens, (iii) presentation of endogenous antigens to MHC-class-1 restricted cytotoxic T lymphocytes (CTLs), (iv) stimulatory capacity in allogeneic mixed-lymphocyte cultures (MLCs), (v) sensitivity to natural-killer (NK)-cell-mediated lysis. Co-culture of EBV-positive BL cells with CD40-ligand-transfected L cells induced up-regulation of CD54 and CD80 but did not affect the expression of viral genes. In spite of significant up-regulation of TAP1 and TAP2, and increased expression of MHC class 1, the BL cells remained unable to present endogenously expressed viral antigens to EBV-specific CTL. However, the up-regulation of adhesion and co-stimulatory molecules was associated with increased stimulatory capacity in MLC and enhanced sensitivity to NK cells. These findings indicate that, while inducing only a modest phenotype shift, cross-linking of CD40 under physiologic conditions may selectively enhance the sensitivity of BL cells to anti-tumor immune responses.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Frisan
authors.forename: D
authors.initials: D
authors.lastname: Donati
authors.forename: L
authors.initials: L
authors.lastname: Cervenak
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: M G
authors.initials: MG
authors.lastname: Masucci
authors.forename: M T
authors.initials: MT
authors.lastname: Bejarano
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D015703:Antigens, CD / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D003432:Cross-Linking Reagents; D003546:Cysteine Endopeptidases / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D009097:Multienzyme Complexes / Q000235:genetics; D046988:Proteasome Endopeptidase Complex
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex