IMMU-11. AN ANALYSIS OF IMMUNOPHENOTYPE, INCLUDING PD-L1 AND PD1 EXPRESSION, IN PEDIATRIC CNS MALIGNANCIES: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY

BACKGROUND: Primary pediatric central nervous system (CNS) malignancies often have poor outcomes despite intensive treatment. Clinical immunotherapeutic trials targeting the programmed cell death receptor (PD-1) and its ligand (PD-L1) have been successful in some cancers. One of the most promising biomarkers for response has been the expression of PD-L1, although this has been not universally predictive and its presence in pediatric CNS tumors remains unknown. METHODS: One hundred formalin-fixed, paraffin embedded samples from children with various pediatric CNS malignancies were collected, including twenty-five of each of the following: ependymoma, high-grade glioma (HGG), supratentorial primitive neuroectodermal tumor (sPNET), and medulloblastoma. Patient characteristics and disease outcomes were also obtained. Chromogenic immunohistochemical staining of PD-L1 and PD1 was completed with prevalence of stained cells scored on a 0–5 scale. ‘Positive’ expression was assigned to scores of three or greater. Gene expression was analyzed using an nCounter Nanostring immunologic gene expression codeset. RESULTS: IHC was successful except in one patient with sPNET and two with HGG. PDL1 expression was robust in a subset of tumors, with ‘positive’ staining in 8 (33%) ependymomas, 4 (17%) high-grade gliomas, 2 (8%) sPNETs, and 0 medulloblastomas; PD1 staining was similarly heterogeneous. RNA extraction and expression analysis was successful in all but one sPNET and one HGG. Hierarchical clustering with respect to genes involved in inflammatory pathways identified distinct subgroups within each tumor type; in particular, medulloblastoma was noted to demonstrate activation of inflammatory genes. PD1/PD-L1 expression data did not correlate with histologic staining. Further analysis of the relationship between clinical information and gene expression is ongoing. CONCLUSIONS: This study demonstrates the tumor-specific PDL1/PD1 expression across tumor types and also provides immunologic phenotypic information that may be useful for future rational immunotherapy development in children with CNS malignancy.