IMMU-04. HIGH FREQUENCY OF PROGRAMMED DEATH LIGAND 1 EXPRESSION IN PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

Tumors escape immune surveillance by activating the inhibitory checkpoint programmed death 1 (PD-1)/programmed death ligand 1 (PDL-1) pathway to attenuate T cell responses and render them functionally exhausted. Antibodies targeting the PD-1/PDL-1 immune checkpoint pathway rescue anti-tumor function and have shown remarkable success in treating several adult cancers, with PDL-1 positive tumors demonstrating the most objective responses. There are limited data on PDL-1 expression in pediatric central nervous system (CNS) tumors. We evaluated PDL-1 expression in formalin-fixed, paraffin-embedded tumor specimens from 37 pediatric patients via immunohistochemistry. We used a rabbit anti-human monoclonal anti PDL-1 antibody by Spring BioSciences (M4424). PDL-1⁺ positivity was quantified as either <1%, 1–5%, 6–25%, 26–50% or >50% membrane staining. Tumors with >5% membrane staining were scored as positive. The proportion of PDL-1⁺ tumors was 100% for anaplastic pleomorphic xanthoastrocytoma (4/4), 80% for pilocytic astrocytoma (4/5), 67% for glioblastoma (4/6), 67% for ependymoma (2/3), 50% for anaplastic astrocytoma (1/2), 50% for primitive neuroectodermal tumor (1/2), 25% for medulloblastoma (1/4), and 0% for pineoblastoma (0/6). Of the remaining 5 tumors tested, 2 were PDL-1⁺ (anaplastic ganglioglioma, anaplastic oligodendroglioma), and 3 were negative for PDL-1 expression (recurrent astrocytoma, atypical choroid plexus papilloma, choroid plexus carcinoma). Interestingly, all glioblastoma tumors (4/4) had >50% PDL-1 expression, whereas all pineoblastoma (6/6) tumors had <1%, showing trends even in a small cohort. Overall, of the 37 tumors tested, 51% (19/37) were PDL-1⁺. Our study reveals strong evidence for an active PD-1/PDL-1 pathway in a high proportion of pediatric CNS tumors. Our next steps are to increase sample size, and evaluate the tumor microenvironment by quantifying tumor infiltrating lymphocytes and regulatory T cells in pediatric CNS tumors to provide support for expediting this targeted immunotherapy in children.