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The expression of T cell subsets was correlated with clinical prognostic parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>The prevalence of CD4<jats:sup>+<\/jats:sup> CD25<jats:sup>+<\/jats:sup> T cells was significantly higher in the TILs than PBLs. The expression of CD4<jats:sup>+<\/jats:sup> CD25<jats:sup>+<\/jats:sup> regulatory T cells in cancer milieu correlated with the tumor grade, stage, and myometrium invasion. The expression of <jats:italic>FOXP3<\/jats:italic> and <jats:italic>GITR<\/jats:italic> in CD4<jats:sup>+<\/jats:sup> CD25<jats:sup>+<\/jats:sup> regulatory T cells was lower in PBLs than TILs. Most tumor\u2010infiltrating CD8<jats:sup>+<\/jats:sup> T cells were CD28<jats:sup>\u2212<\/jats:sup> CD45RA<jats:sup>\u2212<\/jats:sup> CD45RO<jats:sup>+<\/jats:sup> CCR7<jats:sup>\u2212<\/jats:sup>, suggesting good terminal differentiation. Most of them had an activated role with CD69<jats:sup>+<\/jats:sup> CD103<jats:sup>+<\/jats:sup> CD152<jats:sup>+<\/jats:sup>. Functionally, both granzyme B and perforin were scarcely expressed in peripheral regulatory T cells but were highly expressed in peripheral regulatory T cells in the tumor microenvironment. In contrast, CD8<jats:sup>+<\/jats:sup> cytotoxic T cells derived from PBLs expressed both granzyme B and perforin, and at significantly higher levels than in TILs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules can be synchronously up\u2010regulated in CD8<jats:sup>+<\/jats:sup> cytotoxic T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Regulatory T cells in the tumor microenvironment may abrogate CD8<jats:sup>+<\/jats:sup> T cell cytotoxicity in a granzyme B\u2010 and perforin\u2010dependent conduit. Decreases in both Th1 cytokines and cytotoxic enzymes are relevant for regulatory T cell\u2010mediated restraint of tumor clearance in vivo. Of clinical significance, the expression of regulatory T cells in TILs may mediate T cell immune repression within cancer milieu and thus greatly correlate with cancer progression. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25371","type":"journal-article","created":{"date-parts":[[2010,8,29]],"date-time":"2010-08-29T05:32:09Z","timestamp":1283059929000},"page":"5777-5788","source":"Crossref","is-referenced-by-count":47,"title":["Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial 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