Transcriptomes of different glioblastoma cell lines

Myeloid cells, especially monocytes and macrophages, comprise the majority of immune cells within the GB tumor microenvironment (TME), where they contribute to the development of an immunosuppressive milieu hindering potential anti-tumor immune responses. Type I interferons (IFN) usually facilitate a pro-inflammatory shift in monocytes and macrophages and allow for anti-tumor functions.

Using RNA-sequencing, we observed that type I IFN-stimulated genes (ISGs) are globally downregulated in primary human monocytes co-cultured with GB cells both upon direct cell-cell contact and upon the exchange of soluble factors. Surprisingly, the reduction of type I IFN responses did not result from changes in interferon-α/β-receptor (IFNAR) availability and activation. Instead, we identified GM-CSF as a critical, GB cell-derived factor, which decreased ISG expression in monocytes at extremely low concentrations (< 10 pg/mL) via induction of the TGF-β signaling pathway.