CD40 cross-linking enhances the immunogenicity of Burkitt's-lymphoma cell lines

Teresa Frisan, Daria Donati, Laszlo Cervenak, Julia Wilson, Maria Grazia Masucci, Maria Teresa Bejarano

Research output: Article

6 Citations (Scopus)

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-I 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 I, 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.

Original languageEnglish
Pages (from-to)772-779
Number of pages8
JournalInternational Journal of Cancer
Volume83
Issue number6
DOIs
Publication statusPublished - dec. 17 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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