Abstract
Abstract Glioblastoma (GBM) is a grade IV brain tumor that is difficult to manage and associated with high rates of relapse and mortality. Treatment failures are attributed to the blood-brain barrier, increased tumor vascularity, tumor heterogeneity, numerous molecular mutations, and an immunosuppressive microenvironment. The immune microenvironment is comprised of tumor-infiltrating leucocytes (TILs), including several immunosuppressive cell types such as myeloid derived suppressor cells (MDSCs) (immature TILs of myeloid lineage). These tumor supporting immune cells augment the microenvironment and create conditions for immune suppression, contributing to tumor progression and negatively impacting patient survival. The aim of this study was to characterize the TILs in individual patients and correlate these findings with treatment course and survival. We hypothesized that a higher prevalence of MDSCs in tumors would be associated with lower survival rates. In order to investigate this, tumor specimens were collected from GBM patients who underwent tumor resection at Corewell Health (IRB# 2020-024). Fresh GBM samples were collected into tumor storage solution and immediately dissociated into single cell suspensions using a GentleMACS dissociator. The subsequent single cell suspension was stained with a panel of antibodies for TILs and tumor surface markers EGFR and PDGFRA. Flow cytometric analysis of these specimen revealed that the TILs comprising the tumor microenvironment were primarily dominated by CD11b+ myeloid cells, with prevalent MDSCs negatively associated with survival in our study group. Interestingly, MDSCs were negatively correlated with EGFR+ tumor cells while CD3+ T cells were positively correlated. In addition, patients previously treated with either temozolomide or bevacizumab had significantly different TIL immunophenotypes. Together, these data suggest that screening approaches utilizing these techniques may elucidate how tumor cells and TILs may be interacting and reacting to treatment and may provide additional diagnostic and prognostic avenues ultimately leading to improved outcomes for these patients.
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