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Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins

Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-de...

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Autores principales: Grabowski, Matthew M., Watson, Dionysios C., Chung, Kunho, Lee, Juyeun, Bayik, Defne, Lauko, Adam, Alban, Tyler, Melenhorst, Jan Joseph, Chan, Timothy, Lathia, Justin D., Ahluwalia, Manmeet S., Mohammadi, Alireza M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029063/
https://www.ncbi.nlm.nih.gov/pubmed/36945620
http://dx.doi.org/10.1101/2023.03.09.23285970
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author Grabowski, Matthew M.
Watson, Dionysios C.
Chung, Kunho
Lee, Juyeun
Bayik, Defne
Lauko, Adam
Alban, Tyler
Melenhorst, Jan Joseph
Chan, Timothy
Lathia, Justin D.
Ahluwalia, Manmeet S.
Mohammadi, Alireza M.
author_facet Grabowski, Matthew M.
Watson, Dionysios C.
Chung, Kunho
Lee, Juyeun
Bayik, Defne
Lauko, Adam
Alban, Tyler
Melenhorst, Jan Joseph
Chan, Timothy
Lathia, Justin D.
Ahluwalia, Manmeet S.
Mohammadi, Alireza M.
author_sort Grabowski, Matthew M.
collection PubMed
description Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-defined GBM regions in 19 patients with downstream analysis and biobanking, enabling studies of NCE, wherefrom recurrence/progression typically occurs. Immunophenotyping revealed underrepresentation of myeloid cell subsets and CD8+ T cells in the NCE. While NCE T cells phenotypically and functionally resembled those in matching CE tumor, subsets of activated (CD69(hi)) effector memory CD8+ T cells were overrepresented. Contrarily, CD25(hi) Tregs and other subsets were underrepresented. Overall, our study demonstrated that MRI-guided, spatially-registered, intraoperative immunosampling is feasible as part of routine GBM surgery. Further elucidation of the shared and spatially distinct microenvironmental biology of GBM will enable development of therapeutic approaches targeting the NCE infiltrative tumor to decrease GBM recurrence.
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spelling pubmed-100290632023-03-22 Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins Grabowski, Matthew M. Watson, Dionysios C. Chung, Kunho Lee, Juyeun Bayik, Defne Lauko, Adam Alban, Tyler Melenhorst, Jan Joseph Chan, Timothy Lathia, Justin D. Ahluwalia, Manmeet S. Mohammadi, Alireza M. medRxiv Article Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-defined GBM regions in 19 patients with downstream analysis and biobanking, enabling studies of NCE, wherefrom recurrence/progression typically occurs. Immunophenotyping revealed underrepresentation of myeloid cell subsets and CD8+ T cells in the NCE. While NCE T cells phenotypically and functionally resembled those in matching CE tumor, subsets of activated (CD69(hi)) effector memory CD8+ T cells were overrepresented. Contrarily, CD25(hi) Tregs and other subsets were underrepresented. Overall, our study demonstrated that MRI-guided, spatially-registered, intraoperative immunosampling is feasible as part of routine GBM surgery. Further elucidation of the shared and spatially distinct microenvironmental biology of GBM will enable development of therapeutic approaches targeting the NCE infiltrative tumor to decrease GBM recurrence. Cold Spring Harbor Laboratory 2023-03-09 /pmc/articles/PMC10029063/ /pubmed/36945620 http://dx.doi.org/10.1101/2023.03.09.23285970 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Grabowski, Matthew M.
Watson, Dionysios C.
Chung, Kunho
Lee, Juyeun
Bayik, Defne
Lauko, Adam
Alban, Tyler
Melenhorst, Jan Joseph
Chan, Timothy
Lathia, Justin D.
Ahluwalia, Manmeet S.
Mohammadi, Alireza M.
Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title_full Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title_fullStr Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title_full_unstemmed Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title_short Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
title_sort spatial immunosampling of mri-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029063/
https://www.ncbi.nlm.nih.gov/pubmed/36945620
http://dx.doi.org/10.1101/2023.03.09.23285970
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