Glioblastoma Molecular Characteristics and Immune Microenvironment Associated with Survival Outcomes in Patients Treated with Dendritic Cell Vaccination
Purpose:  Autologous tumor lysate-pulsed dendritic cell (DC) vaccination has shown promising long-term survival in a cohort of patients with newly diagnosed glioblastoma.  The purpose of this study was to better understand the mechanisms and modulation of the immune microenvironment underlying the clinical efficacy of DC-based vaccine therapy.  Experimental Design:  We performed bulk RNA sequencing on tumor samples from patients with newly diagnosed glioblastoma obtained prior to treatment with dendritic cell vaccination.  We characterized the molecular mechanisms and immune microenvironments of long-term survivors (LTS, n= 8), medium-term survivors (MTS, n= 13), and short-term survivors (STS, n = 17). Results:  There was an enrichment of the mesenchymal subtype of glioblastoma in the long-term survival group.  Additionally, decreased tumor cell density, upregulation of cell surface markers, and increased neuronal activity were associated with the longer survival cohorts. Two microglia populations, one associated with increased survival and one associated with decreased survival in the DC-treated cohorts, but not standard of care (SOC) cohorts, are also potentially implicated in response to DC immunotherapy. There were increases in functional activity of the immune environment in longer survivor cohorts. Conclusions:  These analyses suggest the potential to identify tumor-based predictive factors that may be associated with favorable responses to DC vaccination in glioblastoma patients; and if validated, these findings may enable better patient selection for future clinical trials. Overall design: The study was designed to understand the molecular characteristics and immune microenvironments of dendric cell vaccine treated patients. Long term survivors of newly diagnosed IDH wild type glioblastoma patients treated with DC vaccine with survival >5year, compared with medium term survivors (3-5 year) and short term survivors to understand the molecular mechanisms and immune microenvironments.