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

• Published in: Journal of leukocyte biology Vol. 102; no. 2; pp. 449 - 458
• Main Authors: Liu, Yu‐feng, Chen, Ying‐ying, He, Ying‐yi, Wang, Jia‐yi, Yang, Jian‐ping, Zhong, Shu‐ling, Jiang, Nan, Zhou, Pan, Jiang, Hua, Zhou, Jie
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.08.2017
• Subjects: Accumulation; Acute lymphoblastic leukemia; Blast cells; CD20 antigen; Cell activation; Children; Contact potentials; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; hematologic malignancies; Humans; immune evasion; Immune system; Immunological tolerance; Immunosuppression; immunosuppressive; Leukemia; Lymphatic leukemia; Lymphocytes B; MDSCs; Minimal residual disease; Myeloid-Derived Suppressor Cells - immunology; Pathogenesis; Patients; Peripheral blood; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Reactive oxygen species; Reactive Oxygen Species - immunology; Real-Time Polymerase Chain Reaction; ROS; S100A9; Signaling; Solid tumors; Stat3 protein; Suppressor cells; Tumor cells; Tumor Escape - immunology; Tumors; hematologic malignancies; MDSCs; immunosuppressive; immune evasion; S100A9; ROS
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.5MA1116-453RR

Accumulation and activation of G‐MDSCs may represent a novel mechanism of immune evasion of tumor cells in B‐ALL patients. 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.