Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas: are these tumors potential candidates for immune check-point blockade?

Brain Tumor Pathol. 2019 Oct;36(4):152-161. doi: 10.1007/s10014-019-00350-1. Epub 2019 Aug 6.


Immune check-point blockade (ICB) targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in cancer treatment. 'ST-RELA' and 'PF-A' molecular subgroups of ependymomas (EPN) show poor outcomes. We aimed to understand the potential candidature of EPNs for ICB. Supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP, and ST-not otherwise specified (NOS), based on RELA/YAP1 fusion transcripts and/or L1CAM and p65 protein expression. Posterior fossa (PF) EPNs were classified into PF-A and PF-B based on H3K27me3 expression. Immunohistochemistry for PD-L1 and CD8 was performed. RelA protein enrichment at PDL1 promoter site was analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR). Eighty-three intracranial EPNs were studied. Median tumor infiltrating CD8 + cytotoxic T-lymphocyte (CTL) density was 6/mm2, and was higher in ST-EPNs (median 10/mm2) as compared to PF-EPNs (median 3/mm2). PD-L1 expression was noted in 17/83 (20%) EPNs, including 12/31 ST-RELA and rare ST-NOS (2/12), PF-A (2/25) and PF-B (1/13) EPNs. Twelve EPNs (14%) showed high CTL density and concurrent PD-L1 positivity, of which majority (10/12) were ST-RELA EPNs. Enrichment of RelA protein was seen at PDL1 promoter. Increased CTL densities and upregulation of PD-L1 in ST-RELA ependymomas suggests potential candidature for immunotherapy.

Keywords: CD8; Ependymoma; Intracranial; Lymphocytes; NF-KB; PD-L1.

MeSH terms

  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Ependymoma / genetics
  • Ependymoma / immunology*
  • Ependymoma / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods
  • Male
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Supratentorial Neoplasms / pathology
  • T-Lymphocytes, Cytotoxic / pathology*
  • Transcription Factor RelA / metabolism


  • B7-H1 Antigen
  • CD274 protein, human
  • L1CAM protein, human
  • Neural Cell Adhesion Molecule L1
  • RELA protein, human
  • Transcription Factor RelA

Supplementary concepts

  • Familial ependymoma