Programmed death ligand-1 (PD-L1) expression in meningioma; prognostic significance and its association with hypoxia and NFKB2 expression

Sci Rep. 2020 Aug 24;10(1):14115. doi: 10.1038/s41598-020-70514-z.

Abstract

Management of clinically aggressive meningiomas is a considerable challenge. PD-L1 induced immune suppression has increasingly gained attention in clinical management of cancer; however, to date, the clinical significance and regulatory mechanisms of PD-L1 in meningioma is not yet fully characterized. We sought to characterize PD-L1 expression in meningioma and elucidate its regulatory mechanisms. Immunohistochemical staining of PD-L1 expression in meningiomas showed 43% positivity in both tumor and immune cells and we observed intra and inter tumoral heterogeneity. Univariate and multivariate analyses confirmed that PD-L1 protein expression is an independent prognostic marker for worse recurrence free survival in meningioma. Furthermore, our transcriptomic analysis revealed a strong association between PD-L1 expression and that of NFKB2 and carbonic anhydrase 9 (CA9). We also demonstrated that both of these markers, when co-expressed with PD-L1, predict tumor progression. Our studies on several meningioma cell lines cultured in hypoxic conditions validated the association of CA9 and PD-L1 expression. Here we show the clinical significance of PD-L1 in meningioma as a marker that can predict tumor recurrence. We also show an association PD-L1 expression with NFKB2 expression and its induction under hypoxic conditions. These findings may open new avenues of molecular investigation in pathogenesis of meningioma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / biosynthesis*
  • Cell Hypoxia / physiology*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Meningeal Neoplasms / pathology*
  • Meningioma / pathology*
  • Middle Aged
  • NF-kappa B p52 Subunit / biosynthesis*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis

Substances

  • Antigens, Neoplasm
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • NF-kappa B p52 Subunit
  • NFKB2 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX