56 Unique Immune Microenvironment in NF2-Fusion Positive Radiation Induced Meningiomas

Abstract

Introduction: Radiation-induced meningiomas (RIMs) are increasing in prevalence as cancer patients live longer. Our laboratory has demonstrated that RIMs have a unique genomic landscape compared to sporadic meningiomas. Notably, a subset of RIMs harbor genomic rearrangement resulting in NF2 gene fusion with a nonrecurrent reciprocal gene. We aimed to compare the gene expression of NF2-Fusion and NF2-Wild Type (NF2-WT) RIMs. Methods: RNA sequencing using Illumina HiSeq was performed on 7 NF2-Fusion and 12 NF2-WT RIMs. Short read sequences obtained from sequencing were mapped to reference human genome(hg19). We performed differential expression analysis using edgeR statistical packages. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was performed to validate findings. Results: Principal component analysis revealed that 5/7 of NF2-Fusion RIMs had similar gene expression profiles. One outlier had no chromosome 1p loss like the other NF2-Fusion RIMs. Pathway analysis demonstrated there was an upregulation of immune pathways in NF2-Fusion RIMs. Immunohistochemistry of PD-L1 revealed that 0/7 and 7/7 of NF2-Fusion tumors had positive expression in tumoral and inflammatory cells, respectively. In comparison, 6/12 of RIMs had tumoral and inflammatory cell expression of PD-L1. In addition, there was a higher CD3 lymphocyte infiltration in NF2-WT (42.2 vs. 12.4 number of cells per HPF). Discussion: Preliminary data in our lab demonstrates that NF2-Fusion tumors have a distinct immune microenvironment compared to NF2-WT tumors. Although pathway analysis indicates that NF2-Fusion RIMs have overexpression of immune pathways, immunohistochemistry reveals that inflammatory cells have positive PD-L1 expression, suggestive of immune burnout.