부산대학교 도서관

Background: An increase of regulatory T cells, defined as CD25- 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 T cells have a higher IL-10/IFN-γ gene expression ratio but express lower levels of TGF-β than CD4 CD25 T cells. Conclusion: We demonstrate strong proliferation among regulatory CD4 FOXP3 CD25 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. [ABSTRACT FROM AUTHOR]