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Hermann, F.* ; Lehr, H.-A.* ; Drexler, I. ; Sutter, G. ; Hengstler, J.* ; Wollscheid, U.* ; Seliger, B.*

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

Cancer Res. 64, 215-220 (2004)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 PA28α and PA28β, 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-γ 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2004
HGF-Berichtsjahr 0
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Zeitschrift Cancer Research
Quellenangaben Band: 64, Heft: 1, Seiten: 215-220 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia, Pa.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-502700-002
DOI 10.1158/0008-5472.CAN-2522-2
Erfassungsdatum 2004-12-21
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