OS10.7.A Activation of the CCR8-ACP5 axis by human microglia/macrophage derived CCL18 promotes glioma growth

Abstract Background Glioblastoma multiforme is a highly malignant primary brain tumor with an average survival of 14 months and very limited therapeutic options. Glioma associated microglia macrophages (GAMs) foster growth by releasing several cytokines, which have only partly been identified. Here, we studied the chemokine (C-C motif) ligand 18 (CCL18), expressed in human, but not rodent GAMs, novel ex-vivo slice model including transplantation human induced pluripotent stem cells (iPSC) derived (iMGL) glioma to murine slices, had depleted intrinsic before. Material Methods After establishing humanized model, performed immunohistochemical analysis (IHC) invasiveness, qrtPCR on isolated magnetic-activated cell sorting (MACS), functional assays measuring proliferation, migration colony formation vitro experiments. Corresponding studies invasiveness were after treatment CCL18 neutralizing antibody, CCR8 antibodies knockdown CCR8, ACP5 (Acid Phosphatase 5) PITPNM3 small interfering RNA (siRNA) short hairpin (shRNA). QrtPCR, IHC Westernblot specimens. We also conducted bioinformatic analyses, based TCGA GBM, GLIOVIS GEPIA databases. Results observed that was whereas cells. identified receptor 8 (CCR8) as for important down-stream signaling component Activation CCL18/CCR8/ACP5 pathway glioblastoma enhanced invasiveness. Conclusion GAMs promoted activation CCR8/ACP5 axis therefore potential target.