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

Oncogene. 2021 Feb;40(8):1516-1530. doi: 10.1038/s41388-020-01627-y. Epub 2021 Jan 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Benzylamines / pharmacology
  • Cell Line, Tumor
  • Cell Migration Inhibition / genetics
  • Chemokine CXCL12 / genetics*
  • Cyclams / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / blood
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Heterografts
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Neoplasm Staging
  • Receptors, CXCR4 / genetics*
  • Signal Transduction / drug effects
  • Tumor Microenvironment / drug effects
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Batf2 protein, human
  • Benzylamines
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclams
  • Receptors, CXCR4
  • Tumor Suppressor Proteins
  • plerixafor