Comparative immunophenotyping of peripheral blood T- and NK-cells of patients with diffuse glioma

Abstract

Peripheral immune profiling in glioblastoma patients revealed profound systemic alterations with features of both immune activation and suppression. Increased T-cell metabolic activity and reduced T-cell exhaustion point to immune activation, while diminished pro-inflammatory cytokines, activated and less exhausted Tregs, and reduced NK cells reflect immune suppression. Recurrent glioblastomas showed even more pronounced abnormalities, including a shift toward TH2 responses, pointing to increasing immune dysfunction with disease progression. Several parameters correlated with patient survival. Higher CD8+CD73+ expression and increased conventional CD4+ T cells were associated with better outcomes, whereas elevated CD8+TIGIT+ and Treg HLA-DR correlated with poorer prognosis. These findings suggest that the dismal prognosis of glioblastoma patients, with a failure of anti-tumor immunity, may result from an imbalance of systemic immune activation and suppression. Targeting this systemic immune dysfunction may provide novel therapeutic opportunities to restore effective anti-tumor immunity in glioblastoma patients. Markers correlating with survival, such as TIGIT, may be of special interest.