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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Zhong, Shu-ling¹  Zhou, Jie¹  Wang, Jia-yi¹  Zhou, Pan¹  Yang, Jian-ping⁶  Jiang, Nan⁶  Jiang, Hua⁶  Chen, Ying-ying⁷  He, Ying-yi^1,10 

[1] and;..Department of Hematology Oncology, Guangzhou Medical University, Affiliated Guangzhou Women and Children's Medical Center, Guangzhou, China;..Institute of Human Virology, Sun Yat‐..Key Laboratory of Tropical Disease Control, Sun Yat‐Department of Hematology Oncology, Guangzhou Medical University, Affiliated Guangzhou Women and Children's Medical Center, Guangzhou, China;Institute of Human Virology, Sun Yat‐Program in Immunology, Zhongshan School of Medicine, Affiliated Guangzhou Women and Children's Medical Center, Guangzhou, China;Sen University, Chinese Ministry of Education, Guangzhou, China;Sen University, Guangzhou, China;Sen University, Hepatic Surgery, Guangzhou, China;The Third Affiliated Hospital of Sun Yat‐

关键词: MDSCs;    immunosuppressive;    S100A9;    ROS;    hematologic malignancies;    immune evasion;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY