Article

Cancer Immunity, Vol. 7, p. 7 (28 March 2007) Submitted: 19 February 2007. Accepted: 19 February 2007.

Increased frequency of regulatory T cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients

Khoon Lin Ling1*, Sarah E. Pratap1*, Gaynor J. Bates2, Baljit Singh3, Neil J. Mortensen3, Bruce D. George3, Bryan F. Warren4, Juan Piris4, Giovanna Roncador5, Stephen B. Fox2, Alison H. Banham2 and Vincenzo Cerundolo1

1Tumor Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom

2Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom

3Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom

4Department of Cellular Pathology, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom

5Monoclonal Antibodies Unit, Biotechnology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain

*These authors contributed equally to this work

Contributed by: V Cerundolo

Keywords: human, colorectal cancer, regulatory T cells, FACS, immunohistochemistry

Abstract

Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients with advanced as compared to early disease. These results support the hypothesis that increased numbers of regulatory T cells in the blood and tumours of colorectal cancer patients may influence the immune response against cancer and suggest that strategies to overcome regulatory T cell activity may be beneficial in the treatment of human colorectal cancer.