Figure 2.

MicroRNAs, exosomes and a nuclear cytokine in microglia/macrophage-glioma interactions. Molecular event ⑩ Tumour supportive CD14+ monocytes and BMDMs downregulate microRNA-146 (miRNA-146) expression; CD14+ BMDM express high levels of Spp1 [35] ⑪ Microglial circKIF18A induces angiogenesis via CircKIF18A-FOXC2 nuclear translocation and ITGB3, CXCR4, and DLL4 transcription while concomitantly activating the PI3K/Akt pathway further promoting angiogenesis and GBM growth [67] ⑫ Let-7 microRNAs containing the sequence motif UUGU can suppress glioma growth through upregulation of TNF-α, MHC I and ICAM1; miRNA oligoribonucleotides that lack the GU-rich core motif may act as a chemoattractant for microglia in glioma [68] ⑬ miR-1246 binding to Telomeric repeat-binding factor 2-interacting protein 1 (TERF2IP) stimulates an immune suppressive phenotype in macrophages (increased CD163, IL-10, IL1RA, TGFβ1 and CCL2 expression, and significantly decreased TNF-α) via STAT3 and NF-κB pathways [69] ⑭ GBM-derived long noncoding RNAs (lnc-TALC) induces TMZ resistance via microglial complement components C5/C5a [70,71] ⑮ Glioma-secreted “hypoxic” exosomal IL-6 and miR-155-3p stimulate autophagy via STAT3 signalling and enhance CD163 and IL-10 expression in macrophages [44] ⑯ Glioma-derived IL-33 enhances activation of AIF1 (Iba1)+ resident microglia and recruitment of CD163+ BMDM [34]; microglial cells in the IL-33+ xenografts also expressed significant levels of IL-33 while upregulating pro-inflammatory cytokines, Spp1 and the lipid metabolism gene, Apoe followed by releasing a notable amount of the monocyte chemoattractant genes (CCL2, CCL3, and CCL12) ⑰ GSC-derived exosomes contain various immunosuppressive molecules that are part of the STAT3 pathway; GSCs-derived exosomes can induce CD163 expression in monocytes [72] Font colour: magenta, “Janus” factors that are secreted by both microglia/macrophages and GBM cells/GSCs (cf. Table 1). “Created with BioRender.com”.