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Increased CTLA-4 and FOXP3 Transcripts in Peripheral Blood Mononuclear Cells of Patients with Breast Cancer

  • Published:
Pathology & Oncology Research

Abstract

Generation of Regulatory T cells (Tregs) is known to play a major role in progression and modulation of the immune escape mechanisms in cancer. These cells express Forkhead/winged helix transcription factor (FOXP3) and also Cytotoxic T-lymphocyte antigen-4 (CTLA-4), as a negative regulatory molecule which, is a potential target for immunotherapy. We, therefore, evaluated FOXP3 and CTLA-4 transcripts in the peripheral blood mononuclear cells from 55 women with histologically-confirmed infiltrating ductal carcinoma of the breast. Blood samples from 40 healthy volunteer women without a history of malignancies or autoimmune disorders were also obtained as a control. The abundance of FOXP3 and CTLA-4 gene transcripts was determined by quantitative real-time PCR (qRT-PCR). Compared to healthy individuals, significantly higher amounts of these transcripts were found in the mononuclear cells from breast cancer patients. Also, a significant correlation was found between CTLA-4 and FOXP3 expressions in a group of patients. Among patients with early stage, nonmetastatic or low-grade disease, the relative expression of CTLA-4 was about 10-fold as much as in the control group. These patients also showed a significant increase, more than 10 fold, in mean relative FOXP3 expression. The results of this investigation point to functional activity of Treg cells in early stages of breast cancer, a finding which emphasizes the significance of Tregs as an imminent target for breast cancer immunotherapy.

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Abbreviations

CTLA-4:

Cytotoxic T-lymphocyte antigen-4

GITR:

Glucocorticoid-induced tumor necrosis factor receptor

TGF-β:

Τransforming growth factor- betta

FoxP3:

Forkhead/winged helix transcription factor

qRT-PCR:

quantitative real-time PCR

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Acknowledgements

This work was funded by grant no. 87-4330 from Shiraz University of Medical Sciences and by Iranian Cancer Network and Shiraz Institute for Cancer Research (ICR-87-505). We also are grateful to the women with and without breast cancer who participated in this project.

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Authors and Affiliations

  1. Cancer Gene Therapy Laboratory, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran

    Mansooreh Jaberipour, Ahmad Hosseini, Abdolrasoul Talei & Abbas Ghaderi

  2. Immunotherapy Laboratory, Department of Immunology, Shiraz University of Medical Sciences, P.O. Box 71345-3119, Shiraz, Iran

    Mojtaba Habibagahi & Saadat Rezai Habibabad

  3. Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran

    Abdolrasoul Talei

  4. Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

    Abbas Ghaderi

Authors
  1. Mansooreh Jaberipour
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  2. Mojtaba Habibagahi
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  3. Ahmad Hosseini
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  4. Saadat Rezai Habibabad
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  5. Abdolrasoul Talei
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  6. Abbas Ghaderi
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Correspondence to Mojtaba Habibagahi.

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Jaberipour, M., Habibagahi, M., Hosseini, A. et al. Increased CTLA-4 and FOXP3 Transcripts in Peripheral Blood Mononuclear Cells of Patients with Breast Cancer. Pathol. Oncol. Res. 16, 547–551 (2010). https://doi.org/10.1007/s12253-010-9256-8

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  • DOI: https://doi.org/10.1007/s12253-010-9256-8

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