Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients

  • Christoph Domschke
  • Florian Schuetz
  • Nora Sommerfeldt
  • Joachim Rom
  • Alexander Scharf
  • Christof Sohn
  • Andreas Schneeweiss
  • Philipp Beckhove
Short Communication

Abstract

Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-γ producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-γ EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A*0201-restricted peptides from the tumor-associated antigens MUC1, Hpa16–24 and Hpa183–191 was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM.

Keywords

Breast cancer Tumor antigen Mucin-1 Bone marrow T cell immunity 

Abbreviations

BM/BMTC

Bone marrow/bone marrow T cell

CA 15-3

Cancer antigen 15-3

CD

Cluster of differentiation

DC

Dendritic cell

EliSpot

Enzyme-linked immunosorbent spot

GM-CSF

Granulocyte macrophage colony-stimulating factor

HIVgag

Human immunodeficiency virus (group-specific antigen)

HLA

Human leukocyte antigen

Hpa/HPSE

Heparanase

IFN-γ

Interferon-γ

IL

Interleukin

MHC

Major histocompatibility complex

MUC1

Mucin-1

NF-κB

Nuclear factor kappa-light-chain enhancer of activated B cells

NOD/SCID

Non-obese diabetic/severe combined immunodeficiency

MAPK

Mitogen-activated protein kinase

PBMC

Peripheral blood mononuclear cell

TA/TAA

Tumor antigen/tumor-associated antigen

TAP

Transporter for antigen presentation

TNF-α

Tumor necrosis factor-α

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Christoph Domschke
    • 1
  • Florian Schuetz
    • 1
  • Nora Sommerfeldt
    • 2
  • Joachim Rom
    • 1
  • Alexander Scharf
    • 1
  • Christof Sohn
    • 1
  • Andreas Schneeweiss
    • 1
  • Philipp Beckhove
    • 2
  1. 1.Department of Gynecology and ObstetricsUniversity Hospital of HeidelbergHeidelbergGermany
  2. 2.Tumor Immunology Program, Division of Translational ImmunologyGerman Cancer Research Center (DKFZ), INF 280HeidelbergGermany

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