Forkhead Box Protein 3 and Regulatory T Cells in Cluster of Differentiation 4 and 8 T cell Subsets in Peripheral Blood of Patients with Breast Cancer

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Radiotherapy and Oncology, Seyed-Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

5 Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Immune cells and their cytokine production affect in the outcomes of many malignancies. Two subsets of cluster of differentiation 4 T cells (TCD4+) are categorized as T helper 1 (TH1) and 2 (TH2) which differ in their cytokine profile. TH1/TH2 cell balance could shift toward TH2-type responsiveness in many malignancies. Regulatory T cells (Treg) are a new group of T cells which are indicated to adjust other immune cells including T helper cells. Forkhead box protein 3 (Foxp3) is a lineage-determining transcription factor for Treg. Several subsets of Foxp3 and Treg have been identified. CD4+Foxp3+Treg and CD8+Foxp3+Treg are the main cell population in circulation and were the subject of evaluation in this study. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 48 patients with breast cancer and 21 healthy controls. Monoclonal antibodies including anti-CD4, anti-CD8 and anti-Foxp3 were used and specific staining process was performed. Flow cytometry was applied for evaluation and assessment of the markers. Findings: The percentage of CD4+Foxp3+Treg was 1.75 ± 0.74 in breast cancer group and 1.25 ± 0.30 in the control group (P = 0.004). The corresponding values for CD8+Foxp3+ Treg were 0.71 ± 0.17 and 0.63 ± 0.16 (P = 0.080). The mean of white blood cell (WBC) count and lymphocyte population in the breast cancer group were lower than the control group but the differences were not statistically significant. Conclusion: According to our findings, altered frequency of Treg might be involved in the prognosis of breast cancer. This may be a contributory factor in the susceptibility to breast cancer. Therefore, targeting Treg can be a novel therapeutic approach in this disease. Keywords: Breast cancer, Regulatory T cells, Foxp3, CD4, CD8, T cells