Abstract 6469: Defining architectural tissue features and cell composition of IDH-mutant gliomas

Abstract This study tests the hypothesis that quantitative profiling of cell type composition and tissue architecture in isocitrate dehydrogenase (IDH)-mutant gliomas can provide valuable insights into tumor aggressiveness, treatment response, and survival. Towards this goal, we have established a novel method to analyze cell composition and tissue architectural features in IDH mutant gliomas based on multiplex immunohistochemistry staining and automated image analysis.Two independent clinically well-annotated TMAs, derived from approximately 200 patients with IDH1-mutant tumors, are being analyzed. A multiplex fluorescence antibody panel was designed to include markers for astrocytes (GFAP+/IDH1-R132H-), glioma cells (IDH1-R132H+), oligodendrocytes (IDH1-R132H-/SOX10+), leukocytes (CD45+), tumor-associated microglia and macrophages (TAMMs) (IBA1+), endothelial cells (CD34+) and perivascular cells (PDGFRß+). QuPath software was employed for image analysis. Statistical analyses were performed using Python.For cell classification we firstly created single-core “ground truth data” from 20 cores by manual/visual training of core-specific cell classifiers. Second, we created a “multiple-core-trained” classifier by training on 10 of the ground truth cores and testing on the remaining 10 cores. Comparison between ground truth data and “multiple-core-trained” data indicated overall cell classification accuracy of 0.8.A pilot-study of 20 tumors demonstrated that the most abundant cell types were glioma cells, while leukocytes and perivascular cells were the least abundant. The abundance of glioma and perivascular cells showed good consistency between cores from the same patient (corr = 0.8 for both). In contrast, the abundance of oligodendrocytes and leukocyte cells was less consistent (corr = 0.4 and 0.3, respectively).Analyses of spatial pairing of cell types demonstrated strongest positive spatial enrichment between endothelial cells and pericytes and between endothelial cells and TAMMs. In contrast, glioma cells and endothelial cells showed negative spatial enrichment. Notably, inside-case concordance for these “pair-metrics” was high (0.8-0.9).Analyses aiming to identify co-regulated “pair-metrics” revealed strong positive correlations between the three pair-metrics TAMMs/perivascular cells, TAMMs/endothelial cells and endothelial cells/perivascular cells indicating inter-case variability of multi-cellular vascular niches."Cell abundance metrics" and "cell pair metrics" are currently being explored for their associations with clinical characteristics and their potential to enhance prognostic value relative to 1p19q status and WHO grades. Citation Format: Elisabet Rodríguez Tomàs, Lina Leiss, Rasul Tabiev, Fredrik Nysjö, Anna Klemm, Carolina Wählby, Thomas Olsson Bontell, Anna Dénes, Asgeir S. Jakola, Anja Smits, Arne Östman. Defining architectural tissue features and cell composition of IDH-mutant gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6469.