Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer

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.

Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model

“…Granzyme B is found to be expressed in breast carcinomas (Hu et al, 2003) and thought to be either protective or work as an immune regulator. More recent reports suggested that granzyme B may contribute to suppression of anti-T cell responses (Lindner et al, 2013) and may be highly expressed in Tregs in the tumor microenvironment (Li et al, 2011). Further mechanistic work to assess the relative levels of each T cell subset in the breast and distant metastatic sites isolated from non-stressed and stressed, and socially isolated mice is ongoing in our laboratory.…”

Further study of circulating IgG antibodies to CD25‐derived peptide antigens in nonsmall cell lung cancer

“…Thus, Treg cells are likely to be involved in the escape of cancer cells from antitumor effector T cells [7]. Increased numbers of Treg cells have been in patients with different types of cancers [8][9][10][11][12]. These observations raise the possibility that a compensatory response to the increased density of Treg cells can be triggered in the body.…”

Organophosphorous Pesticides Metabolite Reduces Human T CD8 Homeostasis and Proliferation by Inducing Cellular Death

“…Indicating that the transduction signal pathway of activation of IL-2 is the main pathway altered by OP compounds in lymphocytes [6]. Besides T CD4 lymphocytes, T CD8 cells have an essential role in some cellular processes, such as the cytotoxic response known as CTL to kill virus and cancer cells.…”

“…Besides T CD4 lymphocytes, T CD8 cells have an essential role in some cellular processes, such as the cytotoxic response known as CTL to kill virus and cancer cells. Therefore, this subset of CD3 lymphocytes are very important as part of the immune response inducing clonal expansion of effectors and memory clones, which are determinant to control pathogens or cancer development [6].…”

“…Besides T CD4 lymphocytes, T CD8 cells have an essential role in some cellular processes, such as the cytotoxic response known as CTL to kill virus and cancer cells. Therefore, this subset of CD3 lymphocytes are very important as part of the immune response inducing clonal expansion of effectors and memory clones, which are determinant to control pathogens or cancer development [6].Actually, it is known that many external insults can affect the immune system and, in fact, it is the target of many xenobiotic agents [7]. Some investigators suggest that the high incidence of certain diseases Abstract Background: We have previously shown that Diethyldithiophosphate (DEDTP), a metabolite of Organophosphorous (OP) compounds biotransformation with longer half life than its parental compound, can modulate T CD4 lymphocyte functions.…”