Journal of Cancer Research and Clinical Oncology

, Volume 132, Issue 4, pp 265–274

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

  • Brigitte Gückel
  • Christine Rentzsch
  • Maria-Dorothea Nastke
  • Alexander Marmé
  • Ines Gruber
  • Stefan Stevanović
  • Simone Kayser
  • Diethelm Wallwiener
Rapid Communication

DOI: 10.1007/s00432-005-0064-6

Cite this article as:
Gückel, B., Rentzsch, C., Nastke, MD. et al. J Cancer Res Clin Oncol (2006) 132: 265. doi:10.1007/s00432-005-0064-6

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-1950–958, MUC-112–20). Antigen-dependent interferon (IFN)-γ 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-1950–958 but not for MUC-112–20. 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-γ 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-1950–958 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-1950–958-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.

Keywords

Mucin MUC-1 Breast cancer Immunotherapy T-cells 

Abbreviations

APC

Antigen presenting cell

BCP

Breast cancer patient

Cpm

Counts per minute

CTL

Cytotoxic T-Lymphocytes

DC

Dendritic cell

DMSO

Dimethylsulfoxid

EBV

Ebstein/barr virus

F

Female

FCS

Fetal calf serum

HCMV

Human cytomegaly virus

HD

Healthy donor

HLA

Human leucocyte antigen

IFN

Interferon

IL

Interleukin

M

Male

MUC-1

Mucin-1

n.t.

Not tested

PBL

Peripheral blood lymphocytes

PBMC

Peripheral blood mononuclear cells

qRT-PCR

Quantitative real time polymerase chain reaction

TAA

Tumor associated antigen

TxNxMx

Clinical classification concerning tumor-, nodal-, and metastases-status

VNTR

Variable number of tandem repeat

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Brigitte Gückel
    • 1
  • Christine Rentzsch
    • 1
  • Maria-Dorothea Nastke
    • 2
  • Alexander Marmé
    • 1
  • Ines Gruber
    • 1
  • Stefan Stevanović
    • 2
  • Simone Kayser
    • 1
  • Diethelm Wallwiener
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity of TübingenTübingenGermany
  2. 2.Department of Immunology, Institute for Cell BiologyUniversity of TübingenTübingenGermany

Personalised recommendations