https://scholars.lib.ntu.edu.tw/handle/123456789/546073
標題: | Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma | 作者: | WEN-CHUN CHANG Li C.-H. Huang S.-C. DAW-YUAN CHANG Chou L.-Y. BOR-CHING SHEU |
公開日期: | 2010 | 卷: | 116 | 期: | 24 | 起(迄)頁: | 5777-5788 | 來源出版物: | Cancer | 摘要: | 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. Copyright ? 2010 American Cancer Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650157267&doi=10.1002%2fcncr.25371&partnerID=40&md5=5abe22447063c52242240cda711562e0 https://scholars.lib.ntu.edu.tw/handle/123456789/546073 |
ISSN: | 0008-543X | DOI: | 10.1002/cncr.25371 | SDG/關鍵字: | CD103 antigen; CD28 antigen; CD45RA antigen; CD45RO antigen; CD69 antigen; chemokine receptor CCR7; cytotoxic T lymphocyte antigen 4; glucocorticoid induced tumor necrosis factor receptor; granzyme B; perforin; transcription factor FOXP3; article; cancer grading; cancer invasion; cancer staging; CD4+ CD25+ T lymphocyte; CD8+ T lymphocyte; controlled study; cytokine production; cytotoxic T lymphocyte; endometrium; endometrium carcinoma; female; human; human cell; immunoregulation; lymphocyte differentiation; major clinical study; myometrium; peripheral lymphocyte; priority journal; prognosis; regulatory T lymphocyte; Th1 cell; tumor associated leukocyte; upregulation; CD8-Positive T-Lymphocytes; Disease Progression; Endometrial Neoplasms; Female; Humans; Immune Tolerance; Lymphocytes, Tumor-Infiltrating; T-Lymphocytes, Regulatory |
顯示於: | 醫學系 |
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