Acute Lymphoblastic Leukemia and Regulatory T cells: Biomarkers and Immunopathogenesis

Abstract

Acute Lymphoblastic Leukemia (ALL) is a hematological malignancy and the most prevalent form of childhood leukemia. Development of ALL is related to the blockade of lymphocyte differentiation, which might affect B or T precursor cells, resulting in the accumulation of blasts in bone marrow. Moreover, immunopathogenesis of ALL involves T regulatory cells (Tregs), which have been investigated in leukemic patients, presenting more immunosuppressive ability than those from normal individuals. Tregs are critical for the maintenance of autoreactive cells, affecting both lineages CD4+ and CD8+, and immune vigilance. Evaluating the role of Tregs in ALL is possible by determining biomarkers related to these cells, such as FOXP3, CD25, CTLA-4 and other molecules that contribute to immunoregulation. In this context, leukemic cells produce ligands that recruit Tregs to the marrow microenvironment, suppressing the antitumor immune response and supporting cancer development. Overall, although Tregs are necessary to inhibit autoreactive T cells, the excessive stimulation of these cells leads to an immunosuppressive state. Immunosuppression in ALL may be partially attributed to the indirect effect of blast cells, which recruit and allow Treg cells to expand, as well as to increase immunosuppressive molecules secreted by both cells. The involvement of Tregs in the immunopathogenesis and their implications in ALL are under the scope of this review and may have important implications in the future. Keywords: Acute Lymphoblastic Leukemia, CD25, CTLA-4, FOXP3, Tregs.