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Homeostasis of peripheral FoxP3+ CD4+ regulatory T cells in patients with early and late stage breast cancer

Cancer Immunology, Immunotherapy volume 59, pages 599–607 (2010)Cite this article

Abstract

FoxP3+ CD4+ regulatory T cells (Tregs) are important mediators of peripheral immune tolerance, acting via multiple mechanisms to suppress cellular immunity including antitumor responses. Although therapeutic strategies have been proposed to deplete Tregs in patients with breast cancer and other malignancies, dynamic changes in the Treg compartment as a function of stage and treatment of breast cancer remain poorly understood. Here, we evaluated peripheral blood CD4+ T cells and FoxP3+ CD4+ T cells from 45 patients with early or late stage breast cancer and compared percentages, absolute counts, and Treg function to those from healthy volunteers (HV) of comparable age. Patients having completed adjuvant chemotherapy and patients with metastatic cancer exhibited significantly lower absolute CD4 counts and significantly higher percentages of FoxP3+ CD4+ T cells. In contrast, the absolute counts of circulating FoxP3+ CD4+ T cells did not differ significantly among early stage patients, late stage patients, or HV. Functionally, FoxP3+ CD4+ T cells from all donor groups similarly expressed CTLA-4 and failed to secrete IFN-γ in response to stimulation. Thus, although Tregs comprise an increased percentage of circulating CD4+ T cells in patients with metastatic breast cancer and patients in remission after completing the adjuvant chemotherapy, the systemic Treg pool, as measured by absolute counts, appears relatively constant regardless of disease stage or treatment status. Total CD4+ T cell counts are not constant, however, suggesting that homeostatic mechanisms, or susceptibility to cytotoxic or malignant insults, fundamentally differ for regulatory and non-regulatory CD4+ T cells.

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Acknowledgments

We thank Theresa Colligon and Adrianna Recio, RN, and Drs. Daniel J. Powell, Jr., Tatiana Golovina, and James Riley for helpful discussions. This study was supported by grants from the Breast Cancer Research Foundation and the NCI (R01 CA111377) and a gift from Mark and Paula Solomon.

Conflict of interest statement

The authors declare that no conflict of interests exist.

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Affiliations

  1. Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 551 BRB II/III, 421 Curie Blvd, Philadelphia, PA, 19104, USA

    Andrew J. Rech & Robert H. Vonderheide

  2. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Rosemarie Mick

  3. Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    David E. Kaplan & Kyong-Mi Chang

  4. Gastroenterology Section, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA

    David E. Kaplan & Kyong-Mi Chang

  5. Division of Hematology-Oncology, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Susan M. Domchek

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  1. Andrew J. Rech
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  2. Rosemarie Mick
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Correspondence to Robert H. Vonderheide.

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Rech, A.J., Mick, R., Kaplan, D.E. et al. Homeostasis of peripheral FoxP3+ CD4+ regulatory T cells in patients with early and late stage breast cancer. Cancer Immunol Immunother 59, 599–607 (2010). https://doi.org/10.1007/s00262-009-0780-x

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  • DOI: https://doi.org/10.1007/s00262-009-0780-x

Keywords

  • Breast cancer
  • Regulatory T cell
  • Clinical trial