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- Title
Glioma exosomes mediate the expansion and function of myeloid‐derived suppressor cells through microRNA‐29a/Hbp1 and microRNA‐92a/Prkar1a pathways.
- Authors
Guo, Xiaofan; Qiu, Wei; Wang, Jian; Liu, Qinglin; Qian, Mingyu; Wang, Shaobo; Zhang, Zongpu; Gao, Xiao; Chen, Zihang; Guo, Qindong; Xu, Jianye; Xue, Hao; Li, Gang
- Abstract
Myeloid‐derived suppressor cells (MDSCs) play a pivotal role in mediating the formation of an immunosuppressive environment and assisting tumors in evading the host immune response. However, the mechanism through which tumors manipulate the differentiation and function of MDSCs remains unclear. Here, we report that hypoxia‐induced glioma cells can stimulate the differentiation of functional MDSCs by transferring exosomal miR‐29a and miR‐92a to MDSCs. Our results showed that glioma‐derived exosomes (GEXs) can enhance the differentiation of functional MDSCs both in vitro and in vivo, and hypoxia‐induced GEXs (H‐GEXs) demonstrated a stronger MDSCs induction ability than did normoxia‐induced GEXs (N‐GEXs). A subsequent miRNA sequencing analysis of N‐GEXs and H‐GEXs revealed that hypoxia‐induced exosomal miR‐29a and miR‐92a expression induced the propagation of MDSCs. miR‐29a and miR‐92a activated the proliferation and function of MDSCs by targeting high‐mobility group box transcription factor 1 (Hbp1) and protein kinase cAMP‐dependent type I regulatory subunit alpha (Prkar1a), respectively. Altogether, the results of our study provide new insights into the role of glioma exosomal miRNAs in mediating the formation of immunosuppressive microenvironments in tumors and elucidate the underlying exosomal miR‐29a/miR‐92a‐based regulatory mechanism responsible for the modulation of functional MDSC induction. What's new? Myeloid derived suppressor cells (MDSC) suppress the immune system, reducing the effectiveness of immunotherapy in various cancers. These authors investigated how hypoxia promotes the immunosuppressive activity of MDSCs. Glioma cells, they found, use exosomes to transport miRNAs to MDSC progenitor cells, stimulating their differentiation. Hypoxia‐induced exosomes exerted a more powerful effect on MDSC proliferation than normoxia‐induced exosomes. The miRNAs induced MDSCs by targeting two genes, Hbp1 and Prkar1a. miRNA silencing of Hbp1 induced the cell cycle progression of MDSCs. This is the first study to demonstrate a mechanism by which glioma cells stimulate MDSC expansion.
- Publication
International Journal of Cancer, 2019, Vol 144, Issue 12, p3111
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.32052