Cellular interactions in the tumor microenvironment have been associated to immunosuppression and the induction of tolerance in the immune system against the tumor. In the immunosuppressive niche, in addition to cancer cells, tumor-associated macrophages (TAMs), glia cells, endothelial cells and T cells also infiltrate the tumor and secrete cytokines, chemokines, and proteases, thus promoting tumor angiogenesis, growth, metastasis, and immunosuppression . The inability to clear the tumor is known, in part, to be a consequence of an immunosuppressive response, with high levels of anti-inflammatory cytokines and reduced expression of T cell activation molecules [35, 38]. However, the mechanisms underlying that immunosuppressive response are not well understood yet, and even less in perivascular areas where tumor cells can infiltrate and metastasize. In this work, we describe a previously unknown immunosuppressive role of brain perivascular pericytes and demonstrate the importance of pericytes’ interaction with tumor cells during GBM progression. Our study reveal that brain pericytes show a pattern of immunosuppressive membrane surface molecule expression in response to GBM cell interaction. Analysis of cytokine expression from GBC-PC also shows high levels of expression of the anti-inflammatory cytokines IL-10 and TGF-β, low level of the pro-inflammatory cytokine TNFα and hardly any production of other important pro-inflammatory cytokines compared to basal levels detected in control pericytes. Interestingly, the increased production of anti-inflammatory cytokines correlates with an upregulation of those cytokines’ gene expression in pericytes, suggesting that pericytes are conditioned by GBM cells (GBC-PC) to produce those cytokines. Our findings indicate that Il1b and Il12 gene expression was not even detected in control pericytes (not shown), and that the mRNA level of Il4, Tnfa and Il23 in pericytes was barely affected by GBM cells. Although protein levels of TNFα are increased in GBC-PC compared to control pericytes, the doubling in amount of protein expression of this pro-inflammatory cytokine (reaching up to 45 pg/ml approximately) is much lower than the protein expression of the anti-inflammatory cytokines TGF-β and IL-10, which reaches higher levels of up to 100 and 400 pg/ml, respectivately in GBC-PC. Interestingly, mRNA and protein expression of the angiogenic cytokine IL-6 released by pericytes in response to neurovascular damage [30, 31] was surprisingly raised in GBC-PC. In a recent study in ovarian cancer, IL-6 was shown to induce defective angiogenesis through altered pericyte coverage in aortic ring vessels . Interestingly, treatment of pericytes with TGF-β has been recently associated with regulation of the neurovascular function, affecting the phagocitic ability of these cells, reducing pericytes proliferation and increasing IL-6 expression . The fact that IL-6 has been associated to an angiogenic gene program in pericytes and even affects pericytes proliferation during angiogenesis in cancer, supports our data and might also explain why we observed a reduced proliferation of GBC-PC in vitro. It is possible that IL-6 expression might be regulated by TGF-β signaling in GBC-PC, attenuating cell proliferation and other neurovascular functions that also affect the tumor progression.