Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma

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.