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

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.