| Summary: | 碩士 === 臺灣大學 === 臨床醫學研究所 === 98 === Background:
To determine the functional attributes of CD4+CD25+regulatory T cells (Tregs) in cancer microenvironment
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Material and Methods:
Triple-color flow cytometry was utilized to study the phenotype expression of CD4+CD25+Tregs and CD8+T-cell in the peripheral blood lymphocytes (PBLs) and tumor infiltrating lymphocytes (TILs) of 30 stage I to III breast cancer.
Results:
The prevalence of CD4+CD25+T cells was significantly higher in the TILs than PBLs. The expression of FOXP3, CD103 and GITR on CD4+CD25+Tregs 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 Tregs but were highly expressed in Treg cells in the tumor micro-environment. On the contrary, CD8+cytotoxic T cells derived from PBLs expressed both granzyme B and perforin, and were significantly higher than those in TILs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules can be synchronously up-regulated in CD8+cytotoxic T cells.
Conclusions:
Tregs 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 Treg-mediated restraint of tumor clearance in vivo. Of clinical significance, the expression of Tregs in TILs may mediate T-cell immune repression within cancer milieu.
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