CD4⁺CD25^highCD127^low/-FoxP₃⁺ Regulatory T-Cell Population in Acute Leukemias: A Review of the Literature

Abstract

Regulatory T-cells (Tregs) are a very important subtype of lymphocytes when it comes to self-control in the human immunological system. Tregs are decisive not only in the protection against destruction of own tissues by autoimmune immunocompetent cells but also in the immunological answer to developing cancers. On the other hand, Tregs could be responsible for the progression of acute and chronic leukemias. In our study, we review publications available in the PUMED database concerning acute leukemia, with a particular emphasis on child’s leukemias. The percentage of regulatory T-lymphocytes in peripheral blood and bone marrow was elevated compared to those in healthy individuals and correlated with progressive disease. Regulatory T-cells taken from children diagnosed with leukemia showed a higher suppressive capability, which was confirmed by detecting elevated levels of secreted IL-10 and TGF-beta. The possibility of pharmacological intervention in the self-control of the immunological system is now under extensive investigation in many human cancers. Presumably, Treg cells could be a vital part of targeted therapies. Routine Treg determination could be used to assess the severity of disease and prognosis in children with acute lymphoblastic leukemia. This proposition results from the fact that in some studies, higher percentage of Treg cells in peripheral blood was demonstrated. However, observations confirming these facts are scarce; thus, extrapolating them to the population of children with hematological malignancies needs to be verified in additional studies.

After Treatment Decrease of Bone Marrow Tregs and Outcome in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia

“…It is widely recognized [ 18 , 37 , 38 ] that BMA-Treg values are higher in, and act at, the neoplastic AML site (i.e., bone marrow) primarily favoring leukemia growth. Additionally, in our study, unlike cytogenetics and molecular AML findings, dBMA Tregs do not correlate with response after antineoplastic treatment, confirming their role in sustaining the disease without being a trigger.…”

Melatonin and Cancer: A Polyhedral Network Where the Source Matters

“…Tregs are decisive, not only in the protection against destruction of own tissues by autoimmune immunocompetent cells, but also in the immunological response to tumor cells. Tregs could be responsible for the progression of acute and chronic leukemias [ 250 ] and have been found increased in patients and animal models of gastric cancer. In this regard, in vivo melatonin administration mediates the downregulation of Foxp3 in Tregs, thus decreasing Treg infiltration in tumor areas as well as reducing tumor growth.…”

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

“…Regulatory T cells (Treg) constitute another part of the immune suppressive leukemia microenvironment. Treg restrain immune competent helper T and cytotoxic T cells through inhibition of T cell proliferation and cytokine production and play an important role in preventing autoreactivity (49, 50). Treg also restrain the activity of B cells (51) and cells of the innate immune system (52, 53).…”