Expansion and activation of granulocytic, myeloid-derived suppressor cells in childhood precursor B cell acute lymphoblastic leukemia.

Abstract

Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies. The role of MDSCs in B-ALL remains poorly understood. Here, we showed that the granulocytic (G)-MDSC population was significantly elevated in both the peripheral blood and BM of patients with B-ALL, when compared with age-matched healthy controls. G-MDSCs levels correlated positively with clinical therapeutic responses and B-ALL disease prognostic markers, including minimal residual disease, and the frequencies of CD20+ and blast cells. The immunosuppressive function of B-ALL-derived G-MDSCs was mediated through the production of reactive oxygen species and required direct cell-cell contact, with the potential participation of STAT3 signaling. Overall, the results of our study support accumulation and activation of G-MDSCs as a novel mechanism of immune evasion of tumor cells in patients with B-ALL and may be a new therapeutic target.