Fig. 1: Schwannomas are comprised of neural crest and immune-enriched molecular groups.

a Hierarchical clustering of the top 2000 most differentially methylated probes from 66 vestibular schwannomas. Significant gene ontology terms corresponding to hypomethylated probes in neural crest schwannomas (NCS) or immune-enriched schwannomas (IES), clinical metadata, and the molecular neuropathology (MNP) DNA methylation classification of central nervous system tumors¹⁶ are shown. b Integrated UMAP of 10,628 transcriptomes from harmonized schwannoma single-nuclei (n = 6) or single-cell (n = 3) RNA sequencing showing schwannoma cell (SC) types and tumor microenvironment cell types. c UMAPs from b with individual transcriptomes split according to a molecular group of origin. d Relative composition of SC types according to a molecular group of origin, colored as in (b). e Scaffold plot comprised of 375,355 Ki67+ immune cells from NCS (n = 3) or IES (n = 3) analyzed using mass cytometry time-of-flight (CyTOF). Manually gated landmark immune cell populations (black) are annotated. Schwannoma immune cell cluster is colored when the proportion of cells is statistically different between IES (positive) and NCS (negative). f CyTOF UMAPs of CD45+ immune cells with overlaid density plots for manually gated myeloid cells (top, 40,000 cells) or CD8 T cells (bottom, 6632 cells) in NCS (left) or IES (right). g UMAP feature plots of marker genes used to define myeloid or CD8 T cells in (f). h CyTOF proportion of schwannoma myeloid cells (left) or CD8 T cells (right) corresponding to M1 macrophages or PD1 + TEMRA CD8 T cells, respectively, in NCS (n = 3 independent tumors) or IES (n = 3 independent tumors). Lines represent means, and error bars represent the standard error of means (two-sided Student’s t-tests, *p = 0.0174, **p = 0.0065). i Representative preoperative magnetic resonance imaging of 66 vestibular schwannomas using T1 post-contrast, T2 diffusion-weighted, or apparent diffusion coefficient (ADC) sequences reveals NCS present as solid masses with reduced diffusion (dotted line) and IES present with cystic changes (arrows) and hydrocephalus. j Nomogram for schwannoma immune enrichment and molecular grouping based on non-invasive clinical and magnetic resonance imaging features. Source data are provided as a Source Data file.