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)|
|Number of pages||12|
|Journal||Journal of neuropathology and experimental neurology|
|State||Published - Jan 1 2020|
Bibliographical noteFunding 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.
© 2019 American Association of Neuropathologists, Inc.
- Immune response
- Low-grade glioma
- Tumor infiltrating immune cells
PubMed: MeSH publication types
- Journal Article