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

Regulatory T cells (T,,g) 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. Treg 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, Treg 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.