Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

Immunopharmacol Immunotoxicol. 2018 Apr;40(2):158-167. doi: 10.1080/08923973.2018.1424897. Epub 2018 Feb 1.

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) which we and others have reported to mediate suppression of anti-tumor immune responses.

Aim: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients.

Methods: Peripheral blood samples withdrawn from B-ALL pediatric patients (n = 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin-HLA-DR-CD33+CD11b+; and Treg cells were defined as CD4+CD25+CD127-/low.

Results: Early diagnosed B-ALL patients showed significant increases in the numbers of MDSCs and Tregs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and Treg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and Treg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy.

Conclusion: Our results indicate that B-ALL patients harbor high numbers of both MDSCs and Tregs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

Keywords: Acute lymphoblastic leukemia; immunosuppressive cells; myeloid-derived suppressor cells; regulatory T cells.

Publication types

  • Clinical Trial

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Myeloid-Derived Suppressor Cells / pathology
  • Pilot Projects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology