Abstract

Immune checkpoint blockade of the programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has shifted the way advanced cancers are treated. The 'ST-RELA fusion positive' and 'PF-A' molecular subgroups of ependymomas (EPN) have a dismal prognosis. AIMS: This study is undertaken to look for immunological microenvironment in ependymomas. Based on L1CAM protein expression and/or the presence of RELA/YAP1 fusion transcripts by RT-PCR, all supratentorial (ST) Grade-II/III EPNs were classified as ST-RELA, ST-YAP, and ST-not otherwise specified (NOS). Based on H3K27me3 protein expression and chromosome 1q gain, all posterior fossa (PF) EPNs were classified as PF-A or PF-B. PD-L1 (SP263, Ventana) and CD8 immunohistochemistry was performed. The enrichment of RelA protein at the PDL1 promoter site was investigated using chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. A total of 83 intracranial EPNs were included in our preliminary data, and we discovered that PD-L1 expression correlates with increasing cytotoxic T-lymphocyte infiltrates in intracranial ependymomas using PD-L1 and CD8 IHC. The majority of PD-L1-positive intracranial EPNs are members of the ST-RELA subset, which also has the highest CTL density. Our findings suggest that ST-RELA EPNs could be used in immunotherapy to target immune checkpoint modulators. To further this research, we are looking into the presence of tumour infiltrating cells such as CD3, CD8, CD163, FOXP3, and others, which can aid in characterising the tumour microenvironment in cell types expressing PD-L1.This study will also be used to predict the prognostic significance of PD-L1/PD1 and other tumour cell infiltrating biomarkers in ependymomas and correlate it with survival outcomes.

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