OS12.7.A Characterization of intra-tumoral heterogeneity and differential immune activation during malignant progression of meningiomas on single cell level

Abstract BACKGROUND As the most common intracranial tumor, meningiomas have caused increasing interest in field of medical research. Based on their mutational profile, can be separated into two main groups: NF2 altered meningiomas, which occur at WHO grades 1 to 3, and non-NF2 mutant with mutations other genes, such as TRAF7, AKT1, KLF4, SMO, are usually grade 1. While this means that follow a benign course, risk stratification for remains difficult. now, underlying mechanisms contributing malignant phenotype some remained unknown, even though molecular markers been associated an increased recurrence. Here, we sought characterize robust subgroups identify critical steps progression these tumors. MATERIAL AND METHODS We applied bulk RNA sequencing proteomic analyses 44 meningioma samples well single nuclei additional set 26 total 46,002 nuclei. Both datasets comprised across landscape 1, 2, 3. RESULTS The previously identified epigenomic level were found consistently also transcriptomic, proteomic, phospho-proteomic levels. In addition, strong differences numbers types infiltrating immune cells between became apparent. A decreased number macrophages activation more proinflammatory was observed 3 This observation correlated lower expression levels CSF1 tumor predicted stimulate 2 Moreover, several cell subpopulations, each defined by distinct phenotype, shared samples. Their proportions strongly depended grade. Especially subpopulation characterized elevated stress response TGFβ signaling activity specifically cases. CONCLUSION Our findings establish multiple characteristic pathway activities demonstrate subtype-specific activation, both may basis novel treatment strategies.