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

Autor:	Moffet JJD; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Fatunla OE; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Freytag L; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia., Kriel J; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Jones JJ; Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia., Roberts-Thomson SJ; Department of Anatomical Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia., Pavenko A; NanoString Technologies Inc., Seattle, Washington, USA., Scoville DK; NanoString Technologies Inc., Seattle, Washington, USA., Zhang L; NanoString Technologies Inc., Seattle, Washington, USA., Liang Y; NanoString Technologies Inc., Seattle, Washington, USA., Morokoff AP; Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia., Whittle JR; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Freytag S; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Best SA; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2023 Nov 01; Vol. 5 (1), pp. vdad142. Date of Electronic Publication: 2023 Nov 01 (Print Publication: 2023).
DOI:	10.1093/noajnl/vdad142
Abstrakt:	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. Competing Interests: S.A.B. received instrument support (GeoMx®) from NanoString Technologies as highlighted in the Acknowledgments section. A.P., D.S., L.Z., and Y.L. are employees and stockholders of NanoString Technologies. (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
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