1. 1,5-AG suppresses pro-inflammatory polarization of macrophages and promotes the survival of B-ALL in vitro by upregulating CXCL14.
- Author
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Wu M, Zhang S, Chi C, Zhu H, Ma H, Liu L, Shi Q, Li D, and Ju X
- Subjects
- Child, Humans, Chemokines, CXC metabolism, Chemokines, CXC pharmacology, Immunotherapy, Tumor Microenvironment, Macrophages metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Abstract
B-lineage acute lymphoblastic leukemia (B-ALL) is one of the most common malignancies in children. Despite advances in treatment, the role of the tumor microenvironment in B-ALL remains poorly understood. Among the key components of the immune microenvironment, macrophages play a critical role in the progression of the disease. However, recent research has suggested that abnormal metabolites may influence the function of macrophages, altering the immune microenvironment and promoting tumor growth. Our previous non-targeted metabolomic detection revealed that the metabolite 1,5-anhydroglucitol (1,5-AG) level in the peripheral blood of children newly diagnosed with B-ALL was significantly elevated. Except for its direct influence on leukemia cells, the effect of 1,5-AG on macrophages is still unclear. Herein, we demonstrated new potential therapeutic targets by focusing on the effect of 1,5-AG on macrophages. We used polarization-induced macrophages to determine how 1,5-AG acted on M1-like polarization and screened out the target gene CXCL14 via transcriptome sequencing. Furthermore, we constructed CXCL14 knocked-down macrophages and a macrophage-leukemia cell coculture model to validate the interaction between macrophages and leukemia cells. We discovered that 1,5-AG upregulated the CXCL14 expression, thereby inhibiting M1-like polarization. CXCL14 knockdown restored the M1-like polarization of macrophages and induced leukemia cells apoptosis in the coculture model. Our findings offer new possibilities for the genetic engineering of human macrophages to rehabilitate their immune activity against B-ALL in cancer immunotherapy., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
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