PT  - JOURNAL ARTICLE
AU  - Betts, Gareth
AU  - Jones, Emma
AU  - Junaid, Syed
AU  - El-Shanawany, Tariq
AU  - Scurr, Martin
AU  - Mizen, Paul
AU  - Kumar, Mayur
AU  - Jones, Sion
AU  - Rees, Brian
AU  - Williams, Geraint
AU  - Gallimore, Awen
AU  - Godkin, Andrew
TI  - Suppression of tumour-specific CD4<sup>+</sup> T cells by regulatory T cells is associated with progression of human colorectal cancer
AID  - 10.1136/gutjnl-2011-300970
DP  - 2012 Aug 01
TA  - Gut
PG  - 1163--1171
VI  - 61
IP  - 8
4099  - http://gut.bmj.com/content/61/8/1163.short
4100  - http://gut.bmj.com/content/61/8/1163.full
SO  - Gut2012 Aug 01; 61
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.