期刊
CANCER LETTERS
卷 506, 期 -, 页码 83-94出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.02.021
关键词
FGL2; Macrophages; Gliomagenesis; CXCL7; CD16
类别
资金
- National Institutes of Health through MD Anderson's Cancer Center Support Grant [P30 CA016672]
- National Institutes of Health [R01 CA120895, R01 CA203493, R01 NS094615]
The study uncovered that in glioma, macrophages promote stem-like phenotypes in cancer cells and immune evasion, showing a close interconnection between the two characteristics in the tumor microenvironment.
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 microenvimnment and induce the macrophages to secrete CXCL7 via the CD16/SyK/PI3K/HIFla 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 antiCXCL7 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.
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