Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer
Journal
Immunologic Research
Journal Volume
51
Journal Issue
1
Pages
71-79
Date Issued
2011
Author(s)
Abstract
Regulatory T (Treg) cells are a subpopulation of T cells with the ability to control the responses of both CD4+ and CD8+ T cells. A case-control study was conducted in order to determine the functional attributes of Treg cells within the breast cancer milieu. Triple-color flow cytometry was utilized to study the phenotype expression of CD4+CD25+ Treg cells and CD8+ T cells in autologous tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) derived from 33 patients with stage I-III breast cancer. The prevalence of CD4+CD25+ T cells was significantly higher in TILs than in PBLs. The expressions of FOXP3 and GITR in CD4+CD25+ Treg cells were lower in PBLs than in TILs. Functional studies showed that both granzyme B and perforin were barely expressed in peripheral Treg cells but were highly expressed in Treg cells in the tumor microenvironment. On the contrary, down-regulation of both granzyme B and perforin expressed in the CD8+ cytotoxic T lymphocytes was significantly lower in TILs than in PBLs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules were synchronously up-regulated in CD8+ cytotoxic T cells. The in vitro kinetic study showed that adequate activation of TILs derived from breast cancer tissue could restore the appropriate antitumor immune response. ? 2011 Springer Science+Business Media, LLC.
SDGs
Other Subjects
gamma interferon; glucocorticoid induced tumor necrosis factor receptor; granzyme B; interleukin 10; interleukin 2; interleukin 4; perforin; transcription factor FOXP3; tumor necrosis factor alpha; article; breast cancer; cancer patient; cancer tissue; case control study; CD4+ CD25+ T lymphocyte; CD8+ T lymphocyte; cellular immunity; clinical article; controlled study; cytokine production; cytotoxic T lymphocyte; down regulation; flow cytometry; human; human cell; human tissue; immunoregulation; in vitro study; peripheral lymphocyte; priority journal; protein expression; regulatory T lymphocyte; T lymphocyte activation; tumor associated leukocyte; tumor immunity; tumor microenvironment; upregulation; Breast Neoplasms; CD8-Positive T-Lymphocytes; Down-Regulation; Female; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Granzymes; Humans; Lymphocyte Activation; Neoplasm Proteins; Neoplasm Staging; Perforin; Retrospective Studies; T-Lymphocytes, Regulatory; Th1 Cells
Type
journal article