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, 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
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.
Conflict of interest statement
The authors declare no competing interests.
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References
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