Abstract
INTRODUCTION: Mass cytometry is a recent technological advance that enables single-cell analysis of the tumor microenvironment, permitting the capture of up to 50 different markers per cell. Tumors of the central nervous system (CNS) in pediatric patients are known to be biologically different from similarly classified adult tumors. Single-cell omics can provide improved understanding of the immune environment in pediatric brain cancers and potentially differentiate them from homonymous adult tumors. METHODS: Using time-of-flight mass cytometry, we compared paired peripheral blood mononuclear cells (PBMCs) and tumor infiltrating CD45+ cells from pediatric patients with medulloblastoma (n = 1), metastatic Ewing sarcoma (n = 1), pediatric high grade glioma (n = 3) and atypical teratoid/rhabdoid tumors (n = 1) to paired PBMCs and tumor samples from 10 adult patients with newly diagnosed glioblastoma. RESULTS: Utilizing multidimensional scaling, we found that samples clustered together based on tumor type. Adult glioblastoma and pediatric high-grade gliomas demonstrated similar proportions of immune populations; medulloblastoma and metastatic Ewing sarcoma had higher proportions of CD4+ and CD8+ T cells compared to adult glioblastoma (adjusted P values < 0.05, general linear hypothesis test). The overall expression of CD27 and CD69 was higher in PBMCs from pediatric patients with high-grade glioma (adjusted P = 0.002 and 0.004, respectively, general linear hypothesis test). CONCLUSIONS: Immune cell populations in pediatric CNS tumors demonstrate distinct compositions in different diseases. Both pediatric high-grade gliomas and adult glioblastomas had similar immune populations with lower proportions of intratumoral T cells than other tumor types, suggesting a more suppressive milieu. However, pediatric high-grade gliomas exhibited increased markers of activation and memory in the periphery compared to their adult counterparts, indicating a more robust systemic immune response. Further exploration using single cell analyses could lead to improved understanding of the tumor microenvironment and targetable mechanisms in pediatric CNS tumors.