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J Cancer Res Clin Oncol. 2006 Apr;132(4):265-74. Epub 2005 Dec 22.

Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers.

Author information

1
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstrasse 7, 72076, Tübingen, Germany. brigitte.gueckel@uni-tuebingen.de

Abstract

PURPOSE:

There is evidence that some tumor patients are able to generate tumor-associated antigen (TAA)-specific T-cell immunity spontaneously. However, little is understood about the existence and nature of self-reactive T-cells that recognize TAA in healthy donors (HD).

METHODS:

Human mucin (MUC-1), a highly glycosylated transmembrane protein, is a well characterized TAA expressed by epithelial tumors. We compared endogenous MUC-1-specific T-cell immunity of breast cancer patients (BCP) and healthy volunteers using two MUC-1-derived HLA-A*0201-restricted peptides (MUC-1(950-958), MUC-1(12-20)). Antigen-dependent interferon (IFN)-gamma and Granzyme B expression of T-cells were analysed by a reverse transcription-polymerase chain reaction (qRT-PCR)-based assay.

RESULTS:

A 32% of BCP and 43% of healthy volunteers revealed pre-existent CD8+ T-cells specific for MUC-1(950-958) but not for MUC-1(12-20). In patients, MUC-1-specific T-cells have been detected mainly in early stage disease prior adjuvant therapy. Those T-cells showed MUC-1-dependent IFN-gamma production after short-term stimulation but no clear Granzyme B expression. However, after repetitive in vitro stimulations using peptide-pulsed CD40-stimulated B-cell lines as autologous antigen presenting cells (APC) T-cell lines exhibited lytic capacity against HLA-A*0201+/MUC-1+ tumor cells.

CONCLUSION:

MUC-1(950-958) is a dominant tumor antigen against which CD8+ T-cells were found frequently in BCP as well as in HD. Until now, this was only known for MelanA/MART-1. In contrast to previous reports, MUC-1-specific immunity was not linked to gender or number of pregnancies in women. Whether MUC-1(950-958)-related immunity highlights a yet unknown cross-reactivity in HD remains unclear. The presence of MUC-1-specific T-cells in some BCP may reflect a balance between immune tolerance and immune defence during aetiopathology.

PMID:
16374613
DOI:
10.1007/s00432-005-0064-6
[Indexed for MEDLINE]

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