RT Journal Article SR Electronic T1 Suppression of tumour-specific CD4+ T cells by regulatory T cells is associated with progression of human colorectal cancer JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1163 OP 1171 DO 10.1136/gutjnl-2011-300970 VO 61 IS 8 A1 Betts, Gareth A1 Jones, Emma A1 Junaid, Syed A1 El-Shanawany, Tariq A1 Scurr, Martin A1 Mizen, Paul A1 Kumar, Mayur A1 Jones, Sion A1 Rees, Brian A1 Williams, Geraint A1 Gallimore, Awen A1 Godkin, Andrew YR 2012 UL http://gut.bmj.com/content/61/8/1163.abstract AB Background There is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4+Foxp3+ regulatory T cells (Tregs) has also been documented.Objective To evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression.Methods A longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4+ T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4.Results Tregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4+ T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4+ T cell responses.Conclusion These findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4+ T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.