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The chemokine <i>CCL5</i>/RANTES is a versatile inflammatory mediator, which interacts with the receptor <i>CCR5</i>, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which <i>CCL5</i> expression correlates with shorter patient survival. Using immunohistochemistry, we identified <i>CCL5</i> and <i>CCR5</i> in a series of glioblastoma samples and cells, including glioblastoma stem cells. <i>CCL5</i> and <i>CCR5</i> gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on <i>CCL5</i>-induced <i>CCR5</i> signaling and is strongly inhibited by the small molecule <i>CCR5</i> antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release <i>CCR5</i> ligands. In support of this model, we detected <i>CCL5</i> and <i>CCR5</i> in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found <i>CCR5</i> expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves <i>CCR5</i> and <i>CCL5</i>, contributing to glioblastoma invasion, suggesting the <i>CCL5</i>/<i>CCR5</i> axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc.