B52
Prognostic value of FOXP3+ T regulatory cell expression in breast cancer
Sahar Mahmoud, Andy Green, Claire Paish, Ian Ellis
University of Nottingham and Nottingham University Hospitals NHS Trust, UK
Background
Studies in mice have shown thymic-derived CD4+ CD25+ regulatory T cells (T reg; FOXP3 lymphocytes) inhibit the antitumour immune response. Additional studies have reported T reg population increases in peripheral blood and tumour tissues from patients with cancer. However,the relationship between the T reg expression and patient prognosis remains controversial. The aim of this study was to determine the prognostic value of FOXP3+ T reg cell density in breast cancer.
Method
Tissue microarrays and immunohistochemistry were used to evaluate the density of FOXP3+ lymphocytes in a series of 1445 cases of well-characterised primary invasive breast carcinomas with long-term follow up. The number of FOXP3+ T cells were counted in tumour nests, in stroma but touching tumour cells, and in stroma not touching tumour cells and relationship with clinical outcome was determined.
Results
A total of 925 tumours (64%) were considered positive for FOXP3+ T cells; 368 tumours (25.5%) were positive for intratumoural FOXP3, 861 tumours (60%) were positive for stromal FOXP3 T cells. The breast cancer specific survival (BCSS) rate for total FOXP3 positive patients was significantly lower than the FOXP3 negative patients (p=0.012 by log-rank test). In addition, positive intratumoural FOXP3 was associated with significantly lower BCSS (p= 0.037). Similarly, FOXP3+ expression in stroma touching tumour cells was associated with lower patient survival (p= 0.001). However, FOXP3 positive T cells in the stroma which were not touching the tumour did not show significant association with BCSS.
Conclusion
These findings indicate that quantification of FOXP3+ T reg in breast cancer is valuable in assessing disease prognosis and FOXP3+ T cell expression within or adjacent to tumour cells is associated with poor patient outcome. This suggests that FOXP3+ T cells could have a role in the suppression of anti-tumour immune response in breast cancer and therefore further studies are warranted.
