Comparative approach to define increased regulatory T cells in different cancer subtypes by combined assessment of CD127 and FOXP3

In recent years an increase of functional CD4⁺CD25⁺ regulatory T cells (T_reg cells) has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4⁺CD25^high T_reg cells in patients with chronic lymphatic leukemia (CLL), multiple myeloma (MM) as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS). In healthy individuals, low-level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with T_reg cells. Here, we demonstrate that the expanded FOXP3⁺ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127^low T _reg cells and were strongly suppressive. A significant portion of CD127^lowFOXP3⁺ T_reg cells expressed only low levels of CD25 suggesting that the previously reported expansion of CD25 ⁺ T_reg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4 ⁺CD127^lowFOXP3⁺T_reg cells revealed an increase of both nave as well as central and effector memory T_reg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of T_reg cells in malignant diseases.