Accumulation of Foxp3+ T Regulatory Cells in Draining Lymph Nodes Correlates with Disease Progression and Immune Suppression in Colorectal Cancer Patients

Purpose: To assess the relation of Foxp3(+) regulatory T cells (Treg) in tumor draining lymph nodes (TDLNs) with tumor progression and immune suppression in colorectal cancer (CRC). Experimental Design: Flow cytometry was used to analyze the densities of Tregs in lymphocytes of TDLNs, peripheral blood, and tumors from 34 patients with CRC. The frequency of Tregs was compared and evaluated for the association with disease stage. The effect of Tregs on the function of CD8(+) T cells was investigated by IFN-gamma production. Results: The density of Foxp3(+) Tregs in TDLNs was dramatically higher than that in peripheral blood lymphocytes, but significantly lower than that in tumor-infiltrating lymphocytes. Importantly, the frequency of Foxp3(+) Tregs in TDLNs, rather than that in tumors and peripheral blood, was positively correlated with disease stage. In addition, the functions of CD8(+) T cells were impaired in TDLNs compared with peripheral blood lymphocytes and were restored after Treg depletion. Conclusions: Foxp3+ Tregs in TDLNs are more correlated with disease progression and potentially influence CD8(+) T-cell functions. This study suggests that the frequency of Tregs in TDLNs may provide a valuable prognostic tool in the treatment of CRC. Clin Cancer Res; 16(16); 4105-12. (C) 2010 AACR.