Work

Tmic-20variations in Arginase 1 Expression in Glioma-associated Microglia and Macrophages

Year: 2015

Type: article

Abstract: Microglia (MG) and macrophages (MP) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MPs function in gliomas, we isolated these cells (and other Gr1+ MDSC) from GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg 1, M2 marker) was highly expressed by tumor-associated Gr1, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg 1 expression in MG was delayed and occurred in larger gliomas. Interestingly, depletion of MP in tumors, did not prevent MG polarization, suggesting direct influence of tumor-specific factors on Arg 1 upregulation. Finally, Arg 1 expression was confirmed in human GBM samples, but most Arg 1+ cells were granulocytes and not MPs. These findings confirm significant variations in tumor MG/MP activation states and its dependency on tumor microenvironmental factors.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/nov236.20