PD-L1 expression in pediatric low-grade gliomas is independent of BRAF V600E mutational status

Allison M. Martin, W. Robert Bell, Ming Yuan, Lauren Harris, Bradley Poore, Antje Arnold, Elizabeth L. Engle, Laura Asnaghi, Michael Lim, Eric H. Raabe, Charles G. Eberhart

Research output: Contribution to journalArticle

Abstract

To evaluate a potential relationship between BRAF V600E mutation and PD-L1 expression, we examined the expression of PD-L1 in pediatric high- and low-grade glioma cell lines as well as a cohort of pediatric low-grade glioma patient samples. Half of the tumors in our patient cohort were V600-wildtype and half were V600E mutant. All tumors expressed PD-L1. In most tumors, PD-L1 expression was low (<5%), but in some cases over 50% of cells were positive. Extent of PD-L1 expression and immune cell infiltration was independent of BRAF V600E mutational status. All cell lines evaluated, including a BRAF V600E mutant xenograft, expressed PD-L1. Transient transfection of cell lines with a plasmid expressing mutant BRAF V600E had minimal effect on PD-L1 expression. These findings suggest that the PD-1 pathway is active in subsets of pediatric low-grade glioma as a mechanism of immune evasion independent of BRAF V600E mutational status. Low-grade gliomas that are unresectable and refractory to traditional therapy are associated with significant morbidity and continue to pose a treatment challenge. PD-1 pathway inhibitors may offer an alternative treatment approach. Clinical trials will be critical in determining whether PD-L1 expression indicates likely therapeutic benefit with immune checkpoint inhibitors.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume79
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • BRAF
  • Immune response
  • Low-grade glioma
  • PD-1
  • PD-L1
  • Tumor infiltrating immune cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Martin, A. M., Bell, W. R., Yuan, M., Harris, L., Poore, B., Arnold, A., Engle, E. L., Asnaghi, L., Lim, M., Raabe, E. H., & Eberhart, C. G. (2020). PD-L1 expression in pediatric low-grade gliomas is independent of BRAF V600E mutational status. Journal of Neuropathology and Experimental Neurology, 79(1), 74-85. https://doi.org/10.1093/jnen/nlz119