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Gut. 2012 Aug;61(8):1163-71. doi: 10.1136/gutjnl-2011-300970. Epub 2011 Dec 29.

Suppression of tumour-specific CD4⁺ T cells by regulatory T cells is associated with progression of human colorectal cancer.

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  • 1Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK.

Abstract

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.

PMID:
22207629
[PubMed - indexed for MEDLINE]
PMCID:
PMC3388728
Free PMC Article

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