BATF2 prevents glioblastoma multiforme progression by inhibiting recruitment of myeloid-derived suppressor cells

• Published in: Oncogene Vol. 40; no. 8; pp. 1516 - 1530
• Main Authors: Zhang, Xin, Liu, Yi, Dai, Lei, Shi, Gang, Deng, Jie, Luo, Qiang, Xie, Qian, Cheng, Lin, Li, Chunlei, Lin, Yi, Wang, Qingnan, Fan, Ping, Zhang, Hantao, Su, Xiaolan, Zhang, Shuang, Yang, Yang, Hu, Xun, Gong, Qiyong, Yu, Dechao, Zheng, Lei, Deng, Hongxin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.02.2021; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/109; 13/21; 13/51; 13/56; 13/89; 14/19; 14/28; 38/44; 59/57; 631/67/1857; 631/80; 64/60; 9/10; 96/31; Adult; Aged; Animals; Apoptosis; Basic-Leucine Zipper Transcription Factors - genetics; Benzylamines - pharmacology; Bone marrow cells; Brain cancer; Care and treatment; Cell Biology; Cell Line, Tumor; Cell Migration Inhibition - genetics; Cellular signal transduction; Chemokine CXCL12 - genetics; Chemotaxis; CXCR4 protein; Cyclams - pharmacology; Development and progression; Extracellular vesicles; Female; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Glioblastoma; Glioblastoma - blood; Glioblastoma - genetics; Glioblastoma - pathology; Glioblastoma multiforme; Glioma cells; Health aspects; Heterografts; Human Genetics; Humans; Inflammation; Internal Medicine; Leucine zipper proteins; Male; Medicine; Medicine & Public Health; Mice; Microenvironments; Middle Aged; Myeloid-Derived Suppressor Cells - metabolism; Myeloid-Derived Suppressor Cells - pathology; Neoplasm Staging; Oncology; Receptors, CXCR4 - genetics; Recruitment; Signal Transduction - drug effects; Stem cells; Suppressor cells; Transcription factors; Tumor Microenvironment - drug effects; Tumor Suppressor Proteins - genetics; Tumors; Young Adult; China
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-01627-y

The basic leucine zipper ATF-like transcription factor 2 (BATF2) has been implicated in inflammatory responses and anti-tumour effects. Little, however, is known regarding its extracellular role in maintaining a non-supportive cancer microenvironment. Here, we show that BATF2 inhibits glioma growth and myeloid-derived suppressor cells (MDSCs) recruitment. Interestingly, extracellular vesicles (EVs) from BATF2-overexpressing glioma cell lines (BATF2-EVs) inhibited MDSCs chemotaxis in vitro. Moreover, BATF2 inhibited intracellular SDF-1α and contributes to decreased SDF-1α in EVs. In addition, BATF2 downregulation-induced MDSCs recruitment were reversed by blocking SDF-1α/CXCR4 signalling upon AMD3100 treatment. Specifically, detection of EVs in 24 pairs of gliomas and healthy donors at different stages revealed that the abundance of BATF2-positive EVs in plasma (BATF2 + plEVs) can distinguish stage III–IV glioma from stage I–II glioma and healthy donors. Taken together, our study identified novel regulatory functions of BATF2 in regulating MDSCs recruitment, providing a prognostic value in terms of the number of BATF2 + plEVs in glioma stage.