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 journalArticlepeer-review

11 Scopus citations


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
Issue number1
StatePublished - Jan 1 2020

Bibliographical note

Funding Information:
The Knights Templar Eye Foundation provided financial support for this study (A.M.M.). This study was supported by Giant Food Pediatric Cancer Re-search Fund, National Cancer Institute Core Grant to the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (P30CA006973), and Bloomberg-Kimmel Institute for Cancer Immunotherapy.

Publisher Copyright:
© 2019 American Association of Neuropathologists, Inc.


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


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