Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma

UK Liyanage, TT Moore, HG Joo, Y Tanaka… - The Journal of …, 2002 - journals.aai.org
UK Liyanage, TT Moore, HG Joo, Y Tanaka, V Herrmann, G Doherty, JA Drebin
The Journal of Immunology, 2002journals.aai.org
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 …
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-β and IL-10 but did not secrete IFN-γ. When cocultured with activated CD8+ cells or CD4+ 25− cells, T reg potently suppressed their proliferation and secretion of IFN-γ. 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.
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