CD4+ regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β

Background An increase of regulatory T cells, defined as CD25 high - and/or FOXP3 + -expressing CD4 + T cells, within tumors has been reported in several studies. Tregs promote tumor growth by modulating the antitumor immune response, mainly through inhibition of T-cell-mediated tumor cell killing: this has been suggested to be dependent on IL-10 and/or TGF-β. In stomach cancer, the mechanisms behind the accumulation of Tregs in tumor tissue has not been fully elucidated, and neither has Treg gene expression in situ. Materials and methods Stomach tissue from gastric cancer patients undergoing gastric resection was analyzed using flow cytometry and cell sorting, followed by RT-PCR. Results We observed that stomach CD4 + FOXP3 + T cells proliferated to a higher degree than CD4 + FOXP3 − T cells, which may contribute to Treg accumulation in the mucosa. By analyzing DNA methylation, we demonstrated that both proliferating and nonproliferating FOXP3 + T cells exhibited complete demethylation of the FOXP3 gene, indicating a stable FOXP3 expression in both cell populations. Furthermore, analysis of T-cell populations isolated directly from the tumor and tumor-free mucosa demonstrated that CD4 + CD25 high T cells have a higher IL-10/IFN-γ gene expression ratio but express lower levels of TGF-β than CD4 + CD25 low/− T cells. Conclusion We demonstrate strong proliferation among regulatory CD4 + FOXP3 + CD25 high T cells in the gastric cancer mucosa. These local Treg express a suppressive cytokine profile characterized by high IL-10 and low TGF-β and IFN-γ production.