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(low)FOXP3(+) 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(low)FOXP3(+) T(reg) cells revealed an increase of both naïve 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.