Increased CTLA-4 and FOXP3 transcripts in peripheral blood mononuclear cells of patients with breast cancer

Pathol Oncol Res. 2010 Dec;16(4):547-51. doi: 10.1007/s12253-010-9256-8. Epub 2010 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis
  • Antigens, CD / blood
  • Antigens, CD / genetics*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • CTLA-4 Antigen
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / blood
  • Forkhead Transcription Factors / genetics*
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Middle Aged
  • RNA, Messenger / blood*
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger