FGL2-wired macrophages secrete CXCL7 to regulate the stem-like functionality of glioma cells

Jun Yan, Qingnan Zhao, Jian Wang, Xiangjun Tian, Jing Wang, Xueqing Xia, Martina Ott, Ganesh Rao, Amy B. Heimberger, Shulin Li

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Glioma stem cells (GSCs) are thought to underlie glioma initiation, evolution, resistance to therapies, and relapse. They are defined by their capacity to initiate glioma in immunocompromised mice which precludes analysis of their interaction with immune cells. Macrophages dominate the immune cell composition in glioma. We hypothesized that stemness and immune evasion induced by macrophages are closed intertwined in glioma. By using mass cytometry and RNA sequencing, we reveal that in immunocompetent mice, FGL2 promotes the stem-like phenotypes of glioma cells in an expression level–dependent manner. Mechanistically, FGL2-producing glioma cells recruit macrophages into the tumor microenvironment and induce the macrophages to secrete CXCL7 via the CD16/SyK/PI3K/HIF1α pathways. CXCL7, in turn, enhances the stem-like functionality of glioma cells, resulting in an increase in tumor incidence and progression that can be blocked with a neutralizing anti-CXCL7 antibody. Clinically, the FGL2-CXCL7 paracrine loop positively correlated with a higher macrophage signature and poorer prognosis in glioma patients. Thus, glioma cells’ stem-like functionality is regulated by FGL2 in the presence of macrophages, and the FGL2-CXCL7 paracrine signaling axis is critical for regulating this function.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalCancer Letters
Volume506
DOIs
StatePublished - May 28 2021

Keywords

  • CD16
  • CXCL7
  • FGL2
  • Gliomagenesis
  • Macrophages

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

MD Anderson CCSG core facilities

  • Flow Cytometry and Cellular Imaging Facility
  • Monoclonal Antibody Facility
  • Research Animal Support Facility
  • Advanced Technology Genomics Core

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