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

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^*

Source：Oncogene, 2021, 40(8): 1516-1530.

DOI：10.1038/s41388-020-01627-y

• STEM-CELLS
• EXTRACELLULAR VESICLES
• CANCER
• INFLAMMATION
• METASTASIS
• ACTIVATION
• AP-1

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-1 alpha and contributes to decreased SDF-1 alpha in EVs. In addition, BATF2 downregulation-induced MDSCs recruitment were reversed by blocking SDF-1 alpha/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.

• Institution
  四川大学; 南方医科大学