Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains

Moffet, JJD; Fatunla, OE; Freytag, L; Kriel, J; Jones, JJ; Roberts-Thomson, SJ; Pavenko, A; Scoville, DK; Zhang, L; Liang, Y; Morokoff, AP; Whittle, JR; Freytag, S; Best, SA

Author(s): Moffet, JJD; Fatunla, OE; Freytag, L; Kriel, J; Jones, JJ; Roberts-Thomson, SJ; Pavenko, A; Scoville, DK; Zhang, L; Liang, Y; Morokoff, AP; Whittle, JR; Freytag, S; Best, SA;
Details: Publication Year 2023,Volume 5,Issue #1,Page vdad142
Journal Title: Neuro-Oncology Advances
Publication Type: epub ahead of print
Abstract: BACKGROUND: High-grade gliomas (HGGs) are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type HGG (glioblastoma, GBM), increased intratumoral heterogeneity is associated with more aggressive disease. METHODS: Spatial technologies can dissect complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. We employed GeoMx digital spatial profiling, CosMx spatial molecular imaging, Xenium in situ mapping and Visium spatial gene expression in experimental and validation patient cohorts to interrogate the transcriptional landscape in HGG. RESULTS: Here, we construct a high-resolution molecular map of heterogeneity in GBM and IDH-mutant patient samples to investigate the cellular communities that compose HGG. We uncovered striking diversity in the tumor landscape and degree of spatial heterogeneity within the cellular composition of the tumors. The immune distribution was diverse between samples, however, consistently correlated spatially with distinct tumor cell phenotypes, validated across tumor cohorts. Reconstructing the tumor architecture revealed two distinct niches, one composed of tumor cells that most closely resemble normal glial cells, associated with microglia, and the other niche populated by monocytes and mesenchymal tumor cells. CONCLUSIONS: This primary study reveals high levels of intratumoral heterogeneity in HGGs, associated with a diverse immune landscape within spatially localized regions.
Publisher: Oxford Academic
Keywords: brain cancer; glioma; immune microenvironment; sequencing; spatial transcriptomics
Research Division(s): Personalised Oncology
PubMed ID: 38077210
Publisher's Version: https://doi.org/10.1093/noajnl/vdad142
Open Access at Publisher's Site: https://doi.org/10.1093/noajnl/vdad142
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-13 10:26:53

Last Modified: 2023-12-13 10:39:05