S.L.); Department of Neuropathology, University of Gö ttingen, Gö ttingen, Germany (U-K.H.); Department of Neurosurgery, Charité Universitä tsmedizin, Berlin, Germany (M.S.); Department of Neurosurgery, Helios Clinic, Berlin, Germany (D.M.) Present affiliation: Neurosurgical Research, Clinic for Neurosurgery, Ludwig Maximilians University of Munich, Munich, Germany (R. G.) Background. Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation in and around the tumor cor-relates with malignancy and poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation of mem-brane type 1 matrix metalloprotease (MT1-MMP). This upregulation depends on signaling via the Toll-like recep-tor (TLR) adaptor molecule myeloid differentiation primary response gene 88 (MyD88). Methods. Using in vitro, ex vivo, and in vivo techniques, we identified TLR2 as the main TLR controlling micro-glial MT1-MMP expression and promoting microglia-assisted glioma expansion. Results. The implantation of mouse GL261 glioma cells into TLR2 knockout mice resulted in significantly smaller tumors, reduced MT1-MMP expression, and en-hanced survival rates compared with wild-type control mice. Tumor expansion studied in organotypic brain slices depended on both parenchymal TLR2 expression and the presence of microglia. Glioma-derived soluble factors and synthetic TLR2 specific ligands induced MT1-MMP expression in microglia from wild-type mice, but no such change in MT1-MMP gene expression was observed in microglia from TLR2 knockout mice. We also found evidence that TLR1 and TLR6 cofunction with TLR2 as heterodimers in regulating MT1-MMP expres-sion in vitro. Conclusions. Our results thus show that activation of TLR2 along with TLRs 1 and/or 6 converts microglia into a glioma supportive phenotype.