TMIC-05. SINGLE-CELL MULTI-OMIC ANALYSIS OF SPORADIC VESTIBULAR SCHWANNOMAS REVEALS SCHWANN CELLS WITH AN INJURY PHENOTYPE AND AN ASSOCIATION BETWEEN TUMOR SIZE AND MACROPHAGE INFILTRATE

Abstract Vestibular schwannomas (VS) comprise 8% of primary brain tumors, with rising prevalence due to increased detection by imaging. How intertumoral heterogeneity and differences within the tumor microenvironment (TME) contribute pathogenesis VS remains poorly understood. We performed single-cell RNA sequencing (scRNA-seq) on 15 sporadic paired single-nucleus assay transposase accessible chromatin (snATAC-seq) 7 tumors. Dimension reduction analysis revealed diverse Schwann, immune—predominantly macrophage, stromal cell populations. Schwann cells adopted multiple unique functional states, such as repair-like, myelinating, hypoxia-response, reflecting undescribed intratumoral VS-associated cells. Remarkably, were found be phenotypically similar in setting peripheral nerve injury, which is robustly associated macrophage recruitment. Indeed, using our scRNA-seq atlas perform deconvolution a broader cohort VS, including newly sequenced (n = 22) published bulk RNA-sequencing datasets 153), we variation proportion immune was strongly correlated infiltrate (R,2 0.86, p < 0.001). Furthermore, that macrophage/monocyte lineage represent disproportionately large number cycling TME, finding corroborated immunohistochemistry. Clinically, tumors high larger size (Fisher’s exact test 0.007). Together, these findings suggest macrophages play an important role pathogenesis. therefore sought characterize potential cell-to-cell interactions between atlas. Ligand-receptor several cytokines expressed cognate receptors macrophages, MIF, SPP1, MDK, SEMA3C IL34, may responsible for recruiting macrophages. In summary, describe previously uncharacterized cellular diversity highlight association infiltration clinical phenotypes, identify therapeutic targets treatment.