Unravelling The Tumor Immune Microenvironment Of Posterior Fossa A Ependymomas On Rna And Protein Expression Levels

Abstract Background Ependymomas account for 8–10% of pediatric brain tumors, and the standard therapy of surgery and radiation has not changed for the past two decades. Characterization of the tumor immune microenvironment (TIME) is of great importance in order to find better therapies. However, the TIME of ependymomas is still not defined. In this retrospective observational study we aimed to unravel the TIME of ependymomas at mRNA and protein expression levels. Methods Ependymoma samples from two locations were selected: Posterior Fossa (PF-A, n=8), and supratentorial (ST, n=5). Targeted gene expression profile using the PanCancer immune profile panel of NanoString technology was performed. Data were analyzed using the nSolver software. In addition, 8 samples were subjected to RNA bulk sequencing, and the sequenced data were connected to the expression data of the same samples. To validate some of the findings, immunohistochemistry was performed. Results Unsupervised hierarchical clustering showed that PF-A ependymomas can be divided into two groups based on the expression of their immune-related genes. PF-A that showed high immune-expression clustered closely to the ST ependymomas. Significant expressions of genes related to “antigen-processing” and “adhesion” pathways were found in the immune-active groups. On the contrary, the PF-A that had low expressions of immune-related genes showed a high expression of BMI1 that has a prognostic and therapeutic value. Connecting gene expression to bulk sequence data validated the findings. In addition, immunohistochemical analysis confirmed that protein expression for some of the findings. Conclusion The TIME varies in ependymomas based on the location of the tumor. Moreover, the immune-related expression profiles indicated that PF-A ependymomas can be divided into two groups: immune-active and immune-not active PF-A. The prognostic and therapeutic values of the immune activity of PF-A should be further studied.