Advances in Brief Increase of Regulatory T Cells in the Peripheral Blood of Cancer Patients

Purpose: T cells constitutively expressing both CD4 and CD25 are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. Experimental Design: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4 CD25 and CD4 CD25 T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. Results: Patients with epithelial malignancies show an increase of CD4 CD25 T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA , CTLA-4 , and transforming growth factor . Notably, CD4 T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25depleted CD4 T cells from control persons by prior removal of CD25 T cells. In contrast to CD4 CD25 T cells, isolated CD4 CD25 T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4 CD25 T cells suppressed the proliferation of CD4 CD25 T cells. When cultured together with CD56 NK-cells, CD4 CD25 T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. Conclusions: Thus, we provide evidence of an increased pool of CD4 CD25 regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.