HER-2/neu-mediated regulation of components of the MHC class I antigen-processing pathway.

Details

Serval ID
serval:BIB_61D49BA34557
Type
Article: article from journal or magazin.
Collection
Publications
Title
HER-2/neu-mediated regulation of components of the MHC class I antigen-processing pathway.
Journal
Cancer Research
Author(s)
Herrmann F., Lehr H.A., Drexler I., Sutter G., Hengstler J., Wollscheid U., Seliger B.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Publication state
Published
Issued date
2004
Volume
64
Number
1
Pages
215-220
Language
english
Abstract
Because of its amplification and/or overexpression in many human tumors, the HER-2/neu proto-oncogene represents an attractive target for T-cell-mediated vaccination strategies. However, overexpression of oncogenes is often associated with defective expression of components of the MHC class I antigen-processing machinery (APM), thereby resulting in an immune escape phenotype of oncogene-transformed cells. To determine whether HER-2/neu influences the MHC class I antigen-processing pathway, the expression pattern of different APM components was examined in murine in vitro models of constitutive and tetracycline-controlled HER-2/neu expression. In comparison with HER-2/neu(-) control cells, HER-2/neu(+) fibroblasts exhibit reduced levels of MHC class I surface antigens that were associated with impaired expression and/or function of the peptide transporter associated with antigen processing, the proteasome subunits low molecular weight protein 2 and low molecular weight protein 10, the proteasome activators PA28alpha and PA28beta, and tapasin. These APM abnormalities resulted in reduced sensitivity to lysis by CTLs. The HER-2/neu-mediated immune escape phenotype could be corrected by IFN-gamma treatment. The clinical relevance of this finding was supported by an inverse correlation between HER-2/neu and the peptide transporter associated with antigen-processing protein expression as determined by immunhistochemical analysis of a series of HER-2/neu(-) and HER-2/neu(+) breast cancer specimens. Thus, a functional link between deficient APM component expression and HER-2/neu overexpression is proposed that might influence the design of HER-2/neu-targeted T-cell-based immunotherapeutic strategies.
Keywords
3T3 Cells, Animals, Gene Expression Regulation/immunology, Histocompatibility Antigens Class I/genetics, Immunotherapy/methods, Mice, Mice, Knockout, Receptor, erbB-2/deficiency, Receptor, erbB-2/genetics, T-Lymphocytes/immunology, Transfection
Pubmed
Create date
28/11/2011 18:44
Last modification date
20/08/2019 14:18
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