Title:Acute Lymphoblastic Leukemia and Regulatory T cells: Biomarkers and Immunopathogenesis
Volume: 12
Issue: 1
Author(s): Carlos H. Hiroki, Rafaela P. Erthal, Ana P.L. Pereira, Letícia M. Pacholak, Thiago C. Fujita, Poliana C. Marinello, Idessânia N. Costa, Sérgio P.D. da Rocha, Maria A.E. Watanabe and Carlos E.C. de Oliveira
Affiliation:
Keywords:
Acute Lymphoblastic Leukemia, CD25, CTLA-4, FOXP3, Tregs.
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.
