Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level

•Increased CD3+ and CD8+ immune-cell infiltration correlates with improved survival.•CD8+CD28-Foxp3+ Tregs are induced in the GBM microenvironment.•Tumor associated APCs display CD8+CD28-Foxp3+ Tregs mediated immunotolerance.•Systemically patients decreased % Th-cells, increased CTLA-4 expression on Th-cells.•GBM patients increased IL-10 plasma concentration compared to healthy controls.

We characterized GBM patients' tumor and systemic immune contexture with aim to reveal the mechanisms of immunological escape, their impact on patient outcome, and identify targets for immunotherapy. Increased CD3+ T-cell infiltration was associated with prolonged survival independent of age, MGMT promoter methylation and post-operative treatment that implies potential for immunotherapy for GBM. Several mechanisms of escape were identified: within the tumor microenvironment: induced CD8+CD28−Foxp3+ Tregs that may tolerize antigen presenting cells, elevated CD73 and CD39 ectonucleotidases that suppress T-cell function, and at the systemic level: elevated IL-10 levels in serum, diminished helper T-cell counts, and upregulated inhibitory CTLA-4.