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Abstract:
Currently there are no therapeutic agents that are effective against both vestibular schwannoma and meningioma, the two most common tumour types affecting patients with the rare tumour predisposition syndrome NF2-related schwannomatosis. This study aimed to characterise the similarities and differences in the tumour immune microenvironments of meningioma and vestibular schwannoma to identify potential therapeutic targets viable for both tumour types. Publicly available bulk Affymetrix expression data for both meningioma (n = 22) and vestibular schwannoma (n = 31) were used to compare gene expression and signalling pathways, and deconvolved to predict the abundance of the immune cell types present. Publicly available single cell RNA sequencing data for both meningioma (n = 6) and vestibular schwannoma (n = 15) was used to further investigate specific T cell and macrophage subtypes for their signalling pathways, gene expression, and drug targets for predicted drug repurposing in both tumour types. Immune cells comprised a larger proportion of the vestibular schwannoma tumour microenvironment compared to meningioma and included a significantly higher abundance of alternatively activated macrophages. However, these alternatively activated macrophages, alongside other immune cell subtypes such as CD8 + T cells and classically activated macrophages, were predicted to be more active in meningioma than vestibular schwannoma. Despite these differences, T cells and tumour associated macrophages of both vestibular schwannoma and meningioma shared drug-target kinases amenable to drug repurposing with Food and Drug Administration (FDA) drugs approved for other conditions. These include bosutinib, sorafenib, mitoxantrone, and nintedanib which are yet to be clinically investigated for vestibular schwannoma or meningioma. Drug repurposing may offer an expedited route to the clinical translation of approved drugs effective for treating both meningioma and vestibular schwannoma to benefit NF2-related schwannomatosis patients.

Keywords:
NF2, NF2-related schwannomatosis, Tumour microenvironment, Inflammation, Vestibular schwannoma, Meningioma, Skull base neoplasm, Tumour associated macrophages, CD8 T cells, TAM