Poster #44: Ijeoma Meremikwu

Transcriptional Heterogeneity of Myeloid Programs in Brain-Invasive Meningioma

Ijeoma C. Meremikwu1,2, Emily Ling-Lin Pai3‡,4, Mingshuang Wang5, Kate Bennet6, Rebecca Ly6, Amy E. Baxter7,8, Christina Jackson5,8, Derek A. Oldridge2,8,9 1Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania; 2Department of Pathology and Laboratory Medicine, Division of Pathology Informatics, Perelman School of Medicine, University of Pennsylvania; 3Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania; 4Department of Pathology and Laboratory Medicine, University of California San Francisco 5Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania; 6Molecular Pathology and Imaging Core, University of Pennsylvania; 7Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania; 8Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania; 9Center for Computational & Genomic Medicine, Children’s Hospital of Philadelphia

Meningiomas are the most common adult central nervous system tumors, with the majority of cases being benign and treatable through a combination of radiotherapy and surgical resection. However, a subset of meningiomas become aggressive and invade adjacent brain tissue, limiting the efficacy of standard treatment and increasing the risk of recurrence. Brain-invasive meningiomas are confirmed by histological review, in which meningioma tissue is seen protruding into the adjacent cortex, with cortical tissue surrounding the invading region. Previous studies have identified CD68+ myeloid populations along the brain-tumor interface (BTI), yet the transcriptional identity of these myeloid cells and the role they play remain unclear. Additionally, prior studies of meningioma brain invasion have profiled either small, specific regions of invasion or larger areas at low resolution, limiting the ability to capture myeloid transcriptional heterogeneity. This leaves open the question of what role myeloid populations play along the BTI in promoting meningioma brain invasion. Here, our goal was to investigate the spatial architecture and transcriptional heterogeneity of myeloid populations enriched along the BTI in brain-invasive meningioma. To this end, we curated a patient cohort of FFPE brain-invasive meningioma tissue samples (n = 3) and performed high-resolution spatial transcriptomics (Visium HD) on two neuropathologist-annotated regions per sample: the BTI region and a non-adjacent tumor-only region. We resolved a set of myeloid transcriptional programs enriched along the BTI and identified their association with BTI-specific meningioma tumor programs. These findings will help to provide insight into the myeloid contribution to meningioma brain invasion.