The Prevalence of FOXP3+ Regulatory T-Cells in Peripheral Blood of Patients with NSCLC

Abstract

We have studied CD4(+)CD25(high)FOXP3(+) regulatory T-cells (T(regs)) from 51 patients with non-small-cell lung cancer (NSCLC) and 33 healthy donors. Regulatory T-cells were identified by fluorescence-activated cell sorting by using a panel of antibodies and by reverse transcriptase polymerase chain reaction analysis for FOXP3 expression. Functional studies were done to analyze their inhibitory role. Finally, regulatory T-cells were analyzed in malignant pleura effusion (PE) from patients with NSCLC. Patients with NSCLC have increased numbers of CD4(+)CD25(high) FOXP3(+) T(regs) in their peripheral blood and pleura effusion (PE), which express high levels of CTLA-4, GITR. These cells were anergic toward T-cell receptor stimulation and, when cocultured with activated CD4(+)CD25(-) cells, potently suppressed their proliferation and cytokine secretion. Our data suggest that in NSCLC patients, there is an increase of CD4(+)CD25(high)FOXP3(+) regulatory T-cells in the peripheral blood and tumor microenvironment. These T-cells might prevent effective antitumor immune responses, and the increase in frequency of CD4(+)CD25(high)FOXP3(+) Tregs might play a role in the modulation of the immune response against NSCLC and could be important in the design of immunotherapeutic approaches.