fig1

Figure 1. The co-evolution of glioblastoma. An increase in the natural evolution signature indicates poor outcome and is emphasized by the progression of cellular subtypes from OPC (oligodendrocyte progenitor-like) to NPC (neural progenitor-like), AC (astrocyte-like), and finally MES (mesenchymal-like). Activation of HIF1A/FOSL2 signaling in tumor cells leads to the secretion of ANXA1, which binds to FPR1/3 on monocyte-derived macrophages (Mo-TAMs), recruiting them to the tumor where they gradually replace the resident microglia-derived macrophages (Mg-TAMs), ultimately resulting in an increasingly immunosuppressive tumor microenvironment. Activated Mo-TAMs secrete CCL2, which, together with the activation of FOSL2 in tumor cells, further increases the invasive potential of GBM cells.