It has been reported that pericytes activated by inflammatory challenge have the ability to present antigen on MHC molecules to T cells, regulating the activity of different T cells populations [16, 20, 21]. We observed that pericytes showed reduced expression of MHC-II molecules and an anti-inflammatory phenotype upon interaction with GBM cells. Therefore, we determined if, in response to GBM interaction, pericytes could instead impair T cell activation. For that purpose, we analyzed the ability of pericytes to present OVA323-339 peptide to T cells, and compared CD4+ T cell responses to peptide presented by GBC-PC with responses to antigen presentation by control pericytes (Figure 3A–3B). We found that pericytes were able to present OVA peptide and activate CD4+ T cells, which led to IL-2 production and cell proliferation. However, pericytes that were interacting with GBM cells showed a significantly impaired ability to activate T cells (Figure 3A–3B). As we had observed that GBC-PC produced high levels of anti-inflammatory cytokines, cytokines, expressed immunosuppresive molecules such as PDL-1 and showed reduced expression of co-stimulatory molecules, we analyzed whether GBM-PC would also affect T cell activation in response to antigen presented by professional antigen presenting cells (APCs). This would support that, when in contact with GBM, pericytes might not only show a reduced ability to cross-present tumor antigens but could also hinder the function of APCs. Corroborating our hypothesis, whereas CD4+ T cells produced high levels of IL-2 and proliferated in response to antigen presented by APCs, those T cells showed defective IL-2 production and proliferation when activated by antigen-loaded APCs in the presence of GBC-PC. T cell activation was not affected by control GBM cells or control pericytes (Figure 3C–3D). To further support that GBC-PC could release anti-inflammatory cytokines to the media that could explain their effect on APC-mediated activation of T cells, we determined whether GBC-PC-conditioned media would also be able to affect T cell activation. We then measured T cell responses to T Cell Receptor (TCR) engagement and co-stimulation, following activation with anti-CD3 and anti-CD28 antibodies, in the presence or absence of culture media from GBC-PC for 72 hours. Importantly, CD4+ T cells showed reduced IL-2 production and proliferation upon TCR and co-stimulation engagement in the presence of GBC-PC-conditioned media when compared to CD4+ T cells activated in presence of control pericyte media or control vehicle. IL-2 secretion and cell proliferation were not affected by control GBM cells (Figure 3E–3F). Importantly, impaired T cell responses caused by GBC-PC were not due to increased apoptosis, as there were no significant differences in cell death percentages between resting or activated T cells cultured with control pericytes or GBC-PC (Supplementary Figure 2). Therefore, our data support that GBC-PC reduces T cell responses through the induction of an anti-inflammatory response and the development of an immunosuppressive phenotype in response to interaction with GBM cells.