Elevated Circulating CD4CD25Foxp3 Regulatory T Cells in Patients with Nonsmall Cell Lung Cancer.

CD4CD25Foxp3 regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4CD25Foxp3 Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4CD25Foxp3 Treg cells and their role in NSCLC. The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. The frequencies of circulating CD4CD25 T cells and CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4CD25Foxp3 Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4CD25Foxp3 Treg cells and CD14 monocytes resulted in a higher frequency of CD206CD14 M2-like monocytes compared with CD14 monocytes. Elevated circulating CD4CD25Foxp3 Treg cells may be involved in the pathogenesis of NSCLC.