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 naive 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.