Abstract
Regulatory T cells (T(reg)) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. In mice, depletion of T(reg) by Ab therapy leads to more efficient tumor rejection. T(reg)-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. In this study, we measured the prevalence of T(reg) that coexpress CD4 and CD25 in the PBLs, tumor-infiltrating lymphocytes, and regional lymph node lymphocytes from 65 patients with either pancreas or breast cancer. In breast cancer patients (n = 35), pancreas cancer patients (n = 30), and normal donors (n = 35), the prevalence of T(reg) were 16.6% (SE 1.22), 13.2% (SE 1.13), and 8.6% (SE 0.71) of the total CD4(+) cells, respectively. The prevalence of T(reg) were significantly higher in breast cancer patients (p < 0.01) and pancreas cancer patients (p < 0.01) when compared with normal donors. In tumor-infiltrating lymphocytes and lymph node lymphocytes, the T(reg) prevalence were 20.2% (SE 3.93) and 20.1% (SE 4.3), respectively. T(reg) constitutively coexpressed CTLA-4 and CD45RO markers, and secreted TGF-beta and IL-10 but did not secrete IFN-gamma. When cocultured with activated CD8(+) cells or CD4(+)25(-) cells, T(reg) potently suppressed their proliferation and secretion of IFN-gamma. We conclude that the prevalence of T(reg) is increased in the peripheral blood as well as in the tumor microenvironment of patients with invasive breast or pancreas cancers. These T(reg) may mitigate the immune response against cancer, and may partly explain the poor immune response against tumor Ags.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abatacept
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Adenocarcinoma / blood
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Adenocarcinoma / immunology*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Aged
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Antigens, CD
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Antigens, Differentiation / biosynthesis
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Breast Neoplasms / blood
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Breast Neoplasms / immunology*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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CD8-Positive T-Lymphocytes / immunology
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CTLA-4 Antigen
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Carcinoma, Ductal, Breast / blood
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Carcinoma, Ductal, Breast / immunology
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Carcinoma, Ductal, Breast / metabolism
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Carcinoma, Ductal, Breast / pathology
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Cell Division / immunology
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Cells, Cultured
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Coculture Techniques
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Cytokines / biosynthesis
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Cytokines / metabolism
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Down-Regulation / immunology
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Female
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Humans
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Immunoconjugates*
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Immunophenotyping
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / metabolism
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Leukocyte Common Antigens / biosynthesis
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Lymphocyte Activation / immunology
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Lymphocyte Count
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Lymphocytes, Tumor-Infiltrating / metabolism
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Lymphocytes, Tumor-Infiltrating / pathology*
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Male
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Middle Aged
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Pancreatic Neoplasms / blood
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Pancreatic Neoplasms / immunology*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Receptors, Interleukin-2 / biosynthesis
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / pathology*
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / pathology*
Substances
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Antigens, CD
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Antigens, Differentiation
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CTLA-4 Antigen
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CTLA4 protein, human
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Ctla4 protein, mouse
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Cytokines
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Immunoconjugates
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Receptors, Interleukin-2
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Abatacept
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Interferon-gamma
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Leukocyte Common Antigens