FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation

Jun Yan, Qingnan Zhao, Konrad Gabrusiewicz, Ling Yuan Kong, Xueqing Xia, Jian Wang, Martina Ott, Jingda Xu, R. Eric Davis, Longfei Huo, Ganesh Rao, Shao Cong Sun, Stephanie S. Watowich, Amy B. Heimberger, Shulin Li

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Few studies implicate immunoregulatory gene expression in tumor cells in arbitrating brain tumor progression. Here we show that fibrinogen-like protein 2 (FGL2) is highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor-cell proliferation in vitro or tumor progression in immunodeficient mice but completely impaired GBM progression in immune-competent mice. This impairment was reversed in mice with a defect in dendritic cells (DCs) or CD103+ DC differentiation in the brain and in tumor-draining lymph nodes. The presence of FGL2 in tumor cells inhibited granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced CD103+ DC differentiation by suppressing NF-κB, STAT1/5, and p38 activation. These findings are relevant to GBM patients because a low level of FGL2 expression with concurrent high GM-CSF expression is associated with higher CD8B expression and longer survival. These data provide a rationale for therapeutic inhibition of FGL2 in brain tumors.

Original languageEnglish (US)
Article number448
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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