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

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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.

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Fig. 1
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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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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Voßstraße 9, 69115, Heidelberg, Germany

    Christoph Domschke, Florian Schuetz, Joachim Rom, Alexander Scharf, Christof Sohn & Andreas Schneeweiss

  2. Tumor Immunology Program, Division of Translational Immunology, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany

    Nora Sommerfeldt & Philipp Beckhove

Authors
  1. Christoph Domschke
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  2. Florian Schuetz
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  3. Nora Sommerfeldt
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  4. Joachim Rom
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  6. Christof Sohn
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  7. Andreas Schneeweiss
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  8. Philipp Beckhove
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Correspondence to Christoph Domschke.

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Domschke, C., Schuetz, F., Sommerfeldt, N. et al. Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients. Cancer Immunol Immunother 59, 479–486 (2010). https://doi.org/10.1007/s00262-009-0801-9

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  • DOI: https://doi.org/10.1007/s00262-009-0801-9

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