Recent experimental and pre-clinical studies show an important role of tumor-infiltrating macrophages in tumor growth, metastasis and response to cancer treatments. Tumor-associated macrophages are attracted by tumor-released molecules which induce reprogramming/differentiation of macrophages into antiinflammatory cells known as alternatively activated, in contrast to inflammatory M1-type macrophages. M2-type macrophages from experimental tumors and various types of cancers express arginase-1, IL-10 and transforming growth factor beta 1, support tumor invasion, angiogenesis and matrix remodelling. The stromal signals influencing glioma progression are poorly known and are likely distinct from those implicated in non-nervous system cancers. Once activated they are characterized by increased chemotaxis, production of inflammation mediators and cytokines, activation of the respiratory burst, and they become immune effector cells mediating both innate and adaptive responses. Histopathologic and flow cytometry studies of human glioma tissue have shown high intratumoral microglia density which correlates with the grade of malignancy. Microglial cells in tumors do not secrete AbMole Corosolic-acid cytokines critical in developing effective innate immune responses and an anti-tumor immune response is suppressed in glioma patients. Several glioma-secreted factors have been characterized as promoting microglial chemotaxis: macrophage colony-stimulating factor 1, granulocyte/macrophage colony-stimulating factor, hepatocyte growth factor and monocyte chemotactic protein 3. Immunosuppressive properties of glioma cancer stem cells, producing CSF-1, TGF-b1 and macrophage inhibitory cytokine, and inducing polarisation of recruited macrophages/microglia have been demonstrated. Experimental studies using brain organotypic slices depleted of microglia, genetic models of microglia ablation and microgliaglioma co-cultures pinpoint a pro-invasive role of gliomainfiltrating microglia. Glioma-exposed microglia release metalloproteinase MT1-MMP which activates a latent metalloproteinase 2 produced by glioma cells that promotes tumor invasion, as was shown using brain slices from MT1-MMPdeficient mice and in a microglia depletion model. Furthermore, microglial cells secrete active TGF-b1, which stimulates glioblastoma invasion. In the present study, we demonstrate that microglia and macrophages accumulate in GL261 experimental gliomas, adapt an anti-inflammatory ��M2�� phenotype, express arginase-1, IL-10 and MMPs. To interfere with glioma-microglia interactions, we used cyclosporine A which has been shown to reduce microglia activation and invasion of glioma cells in vitro and in organotypic brain slices. Systemically-applied CsA inhibits microglia/macrophage infiltration, induces cell death of infiltrating cells and blocks expression/activity of enzymes and cytokines, important for the establishment of a pro-invasive AbMole QS11 phenotype of glioma-infiltrating microglia/macrophages.