Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma.

06:23 EST 21st December 2014 | BioPortfolio

Summary of "Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma."


BACKGROUND:
: A study was carried out to determine the functional attributes of CD4(+) CD25(+) regulatory T cells in cancer progression by suppressing antitumor immunity.
METHODS:
: Triple-color flow cytometry was used to study the phenotype expression of CD4(+) CD25(+) regulatory T cells and CD8(+) T cells in the peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) of 57 cases of stage I to IV endometrial carcinoma. The expression of T cell subsets was correlated with clinical prognostic parameters.
RESULTS:
: The prevalence of CD4(+) CD25(+) T cells was significantly higher in the TILs than PBLs. The expression of CD4(+) CD25(+) regulatory T cells in cancer milieu correlated with the tumor grade, stage, and myometrium invasion. The expression of FOXP3 and GITR in CD4(+) CD25(+) regulatory T cells was lower in PBLs than TILs. Most tumor-infiltrating CD8(+) T cells were CD28(-) CD45RA(-) CD45RO(+) CCR7(-), suggesting good terminal differentiation. Most of them had an activated role with CD69(+) CD103(+) CD152(+). 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(+) 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-regulated in CD8(+) cytotoxic T cells.
CONCLUSIONS:
: Regulatory T cells in the tumor microenvironment may abrogate CD8(+) T cell cytotoxicity in a granzyme B- and perforin-dependent conduit. Decreases in both Th1 cytokines and cytotoxic enzymes are relevant for regulatory T cell-mediated 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. (c) 2010 American Cancer Society.

Affiliation

Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.

Journal Details

This article was published in the following journal.

Name: Cancer
ISSN: 0008-543X
Pages:

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