Abstract 5498: Multi-modal examination of spatial heterogeneity in the astrocytoma microenvironment

Abstract Astrocytoma is a diffuse tumor that infiltrates the brain. Despite post-operative therapy including radiation and chemotherapy, 52% of patients’ tumors recur within five-years of surgery. These tumors are characterized by mutations in the IDH1 or IDH2 gene that confer metabolic alterations, most notably the production of the onco-metabolite 2-hydroxyglutarate. To reveal the metabolic alterations and their upstream regulation across the tumor microenvironment, we applied spatial metabolomics and spatial transcriptomics to sequential sections from resected tumor samples of patients with low grade astrocytoma. This necessitated extensive optimization of atmospheric-pressure MALDI-TOF, including the establishment of a custom automated computational pipeline with abilities to identify metabolic niches. Additionally, using sequential sections of the same tumor, we also compared all commercially available imaging-based spatial transcriptomic technologies (10x Genomics Xenium, Nanostring CosMx, Vizgen MERSCOPE) to evaluate their suitability with regards to building a multi-modal model of metabolic activity and regulation across the tumor microenvironment. We found that 10x Genomics Xenium was most suited for this task as image registration across sequential sections was comparatively straight-forward. Combining spatial transcriptomics generated with 10x Genomics Xenium and spatial metabolomics across 8 matched sequential slices of the same tumor, we identified metabolic niches associated with distinct cell type composition and transcriptional regulation. Citation Format: Joel Moffet, Jurgen Kriel, Tianyao Lu, Lutz Freytag, James Whittle, Sarah Best, Saskia Freytag. Multi-modal examination of spatial heterogeneity in the astrocytoma microenvironment abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5498.