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CD40 cross‐linking enhances the immunogenicity of Burkitt's‐lymphoma cell lines
Author(s) -
Frisan Teresa,
Donati Daria,
Cervenak Laszlo,
Wilson Julia,
Masucci Maria Grazia,
Bejarano Maria Teresa
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991210)83:6<772::aid-ijc13>3.0.co;2-g
Subject(s) - biology , cytotoxic t cell , antigen , cd40 , ctl* , mhc class i , major histocompatibility complex , immunogenicity , cd80 , immunology , burkitt's lymphoma , virology , microbiology and biotechnology , lymphoma , cd8 , in vitro , biochemistry
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. Int. J. Cancer 83:772–779, 1999. © 1999 Wiley‐Liss, Inc.