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OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. GBM remains an incurable disease, with a median survival ~20 months. Complex intercellular interactions within the tumor microenvironment and spatial heterogeneity have challenged and impeded therapeutic effic...

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Autores principales: Watson, Dionysios C, Bayik, Defne, Grabowski, Matthew, Ahluwalia, Manmeet, Mohammadi, Alireza, Lathia, Justin D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264919/
http://dx.doi.org/10.1093/noajnl/vdab070.041
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author Watson, Dionysios C
Bayik, Defne
Grabowski, Matthew
Ahluwalia, Manmeet
Mohammadi, Alireza
Lathia, Justin D
author_facet Watson, Dionysios C
Bayik, Defne
Grabowski, Matthew
Ahluwalia, Manmeet
Mohammadi, Alireza
Lathia, Justin D
author_sort Watson, Dionysios C
collection PubMed
description BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. GBM remains an incurable disease, with a median survival ~20 months. Complex intercellular interactions within the tumor microenvironment and spatial heterogeneity have challenged and impeded therapeutic efficacy. The non-contrast-enhancing (by T1-weighted MRI) rim of GBM is not always safely resectable and represents a major source of recurrence. We hypothesized that differential immune infiltration is an underlying factor of spatial heterogeneity in GBM, particularly in the non-contrast-enhancing tumor rim. METHODS: Five patients with newly diagnosed GBM (ages 53–84) were recruited to a device feasibility study (NCT04545177) utilizing an intraoperative high-resolution MRI-based navigation system coupled with the NICO Myriad (a non-ablative semi-automated resection tool) and a coupled automated biological Tissue Preservation System (NICO APS) to sample spatially mapped regions of tumors in a reproducible and minimally destructive manner. We obtained brain tumor tissue from: (a) tumor core, (b) contrast-enhancing tumor rim and (c) non-contrast-enhancing tumor rim. Downstream processing consisted of digestion of tumor tissue (Miltenyi human tumor digestion kit) for subsequent single-cell isolation, viability assessment and immediate staining for multiparametric flow cytometry for immune profiling. RESULTS: Viability varied across sampled regions (median 85%, range 52–100%). With the exception of 1 sample, viability was >70% in all specimens. High-dimensional analysis with 26 marker flow cytometry revealed spatial heterogeneity in the frequency of myeloid-derived suppressor cell subsets, regulatory T cells, CD8+ T cells, as well as expression of T cell activation and exhaustion markers. CONCLUSIONS: Semi-automated, spatially mapped intraoperative sampling of GBM with high viability of specimens is feasible and reproducible with the NICO Myriad and APS devices. High-dimensional analysis of immune cells in the GBM microenvironment captured the spatial heterogeneity of GBM. Future studies will expand on these observations by analyzing more patient specimens in combination with multiple omics assays.
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spelling pubmed-82649192021-07-08 OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims Watson, Dionysios C Bayik, Defne Grabowski, Matthew Ahluwalia, Manmeet Mohammadi, Alireza Lathia, Justin D Neurooncol Adv Supplement Abstracts BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. GBM remains an incurable disease, with a median survival ~20 months. Complex intercellular interactions within the tumor microenvironment and spatial heterogeneity have challenged and impeded therapeutic efficacy. The non-contrast-enhancing (by T1-weighted MRI) rim of GBM is not always safely resectable and represents a major source of recurrence. We hypothesized that differential immune infiltration is an underlying factor of spatial heterogeneity in GBM, particularly in the non-contrast-enhancing tumor rim. METHODS: Five patients with newly diagnosed GBM (ages 53–84) were recruited to a device feasibility study (NCT04545177) utilizing an intraoperative high-resolution MRI-based navigation system coupled with the NICO Myriad (a non-ablative semi-automated resection tool) and a coupled automated biological Tissue Preservation System (NICO APS) to sample spatially mapped regions of tumors in a reproducible and minimally destructive manner. We obtained brain tumor tissue from: (a) tumor core, (b) contrast-enhancing tumor rim and (c) non-contrast-enhancing tumor rim. Downstream processing consisted of digestion of tumor tissue (Miltenyi human tumor digestion kit) for subsequent single-cell isolation, viability assessment and immediate staining for multiparametric flow cytometry for immune profiling. RESULTS: Viability varied across sampled regions (median 85%, range 52–100%). With the exception of 1 sample, viability was >70% in all specimens. High-dimensional analysis with 26 marker flow cytometry revealed spatial heterogeneity in the frequency of myeloid-derived suppressor cell subsets, regulatory T cells, CD8+ T cells, as well as expression of T cell activation and exhaustion markers. CONCLUSIONS: Semi-automated, spatially mapped intraoperative sampling of GBM with high viability of specimens is feasible and reproducible with the NICO Myriad and APS devices. High-dimensional analysis of immune cells in the GBM microenvironment captured the spatial heterogeneity of GBM. Future studies will expand on these observations by analyzing more patient specimens in combination with multiple omics assays. Oxford University Press 2021-07-05 /pmc/articles/PMC8264919/ http://dx.doi.org/10.1093/noajnl/vdab070.041 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Supplement Abstracts
Watson, Dionysios C
Bayik, Defne
Grabowski, Matthew
Ahluwalia, Manmeet
Mohammadi, Alireza
Lathia, Justin D
OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title_full OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title_fullStr OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title_full_unstemmed OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title_short OTEH-2. High-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
title_sort oteh-2. high-dimensional analysis of spatial immune cell heterogeneity in glioblastoma reveals differences between contrast-enhancing and non-contrast-enhancing tumor rims
topic Supplement Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264919/
http://dx.doi.org/10.1093/noajnl/vdab070.041
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