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 language | English (US) |
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Pages (from-to) | 74-85 |
Number of pages | 12 |
Journal | Journal of neuropathology and experimental neurology |
Volume | 79 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2020 |
Keywords
- BRAF
- Immune response
- Low-grade glioma
- PD-1
- PD-L1
- Tumor infiltrating immune cells
ASJC Scopus subject areas
- General Medicine