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


CONCLUSIONS
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.
Gückel
Brigitte
B
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstrasse 7, 72076, Tübingen, Germany. brigitte.gueckel@uni-tuebingen.de
Rentzsch
Christine
C
Nastke
Maria-Dorothea
MD
Marmé
Alexander
A
Gruber
Ines
I
Stevanović
Stefan
S
Kayser
Simone
S
Wallwiener
Diethelm
D
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002277:Carcinoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; C520326:MUC-1 protein, human (950-958); C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D010446:Peptide Fragments