Immune classifications with cytotoxic CD8+ and Th17 infiltrates are predictors of clinical prognosis in glioblastoma

Abstract

Background: Interest is growing on immune cells involvement in central nervous system tumors such as glioblastoma. Even if a few reports highlighted that immune classifications could have a prognostic value, no paradigm has been clearly yet established on large and homogeneous cohorts. The aim of our study was to analyze the prognostic role of the in situ immune response of cytotoxic T cells (i.e., CD8+), Foxp3 cells, Th17 and tumor-associated macrophages in glioblastoma on two independent large and homogeneous cohorts. Methods: We worked on two large homogenous cohorts of patients having glioblastoma who underwent standard radiochemotherapy. The first cohort of 186 patients was analyzed using IHC procedures (CD8+, IL-17A, FoxP3 and CD163) of surgery pieces. We next worked with transcriptomic data available online and used metagene strategy analysis for the second cohort of 525 patients. Results: Cytotoxic CD8+ lymphocytes and Foxp3 cells were associated with a good prognosis, while Th17 were associated with a poor clinical outcome. These data were confirmed with transcriptomic analysis. Moreover, we showed for the first time a strong link between angiogenesis and Th17 metagenes expressions in glioblastoma. Conclusions: Our study shows that glioblastoma bearing patients can be classified on the immune infiltrate aspects. Beyond this prognostic role of immune biomarkers, subsequent classifications could definitely help clinicians to handle targeted therapy administration and immunotherapeutic interventions.