Cranioencephalic functional lymphoid units in glioblastoma

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxta...

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Hauptverfasser: Dobersalske, Celia Christina (VerfasserIn) , Rauschenbach, Laurèl (VerfasserIn) , Hua, Yichao (VerfasserIn) , Berliner, Christoph (VerfasserIn) , Steinbach, Anita (VerfasserIn) , Grüneboom, Anika (VerfasserIn) , Kokkaliaris, Konstantinos D. (VerfasserIn) , Heiland, Dieter H. (VerfasserIn) , Berger, Pia (VerfasserIn) , Langer, Sarah (VerfasserIn) , Tan, Chin Leng (VerfasserIn) , Stenzel, Martin (VerfasserIn) , Landolsi, Somaya (VerfasserIn) , Weber, Flora (VerfasserIn) , Darkwah Oppong, Marvin (VerfasserIn) , Werner, Rudolf A. (VerfasserIn) , Gull, Hanah (VerfasserIn) , Schröder, Thomas (VerfasserIn) , Linsenmann, Thomas (VerfasserIn) , Buck, Andreas K. (VerfasserIn) , Gunzer, Matthias (VerfasserIn) , Stuschke, Martin (VerfasserIn) , Keyvani, Kathy (VerfasserIn) , Forsting, Michael (VerfasserIn) , Glas, Martin (VerfasserIn) , Kipnis, Jonathan (VerfasserIn) , Steindler, Dennis A. (VerfasserIn) , Reinhardt, Hans Christian (VerfasserIn) , Green, Edward W. (VerfasserIn) , Platten, Michael (VerfasserIn) , Tasdogan, Alpaslan (VerfasserIn) , Herrmann, Ken (VerfasserIn) , Rambow, Florian (VerfasserIn) , Cima, Igor (VerfasserIn) , Sure, Ulrich (VerfasserIn) , Scheffler, Björn (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2024
In: Nature medicine
Year: 2024, Jahrgang: 30, Heft: 10, Pages: 2947-2956
ISSN:1546-170X
DOI:10.1038/s41591-024-03152-x
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-024-03152-x
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41591-024-03152-x
Volltext
Verfasserangaben:Celia Dobersalske, Laurèl Rauschenbach, Yichao Hua, Christoph Berliner, Anita Steinbach, Anika Grüneboom, Konstantinos D. Kokkaliaris, Dieter H. Heiland, Pia Berger, Sarah Langer, Chin L. Tan, Martin Stenzel, Somaya Landolsi, Flora Weber, Marvin Darkwah Oppong, Rudolf A. Werner, Hanah Gull, Thomas Schröder, Thomas Linsenmann, Andreas K. Buck, Matthias Gunzer, Martin Stuschke, Kathy Keyvani, Michael Forsting, Martin Glas, Jonathan Kipnis, Dennis A. Steindler, Hans Christian Reinhardt, Edward W. Green, Michael Platten, Alpaslan Tasdogan, Ken Herrmann, Florian Rambow, Igor Cima, Ulrich Sure and Björn Scheffler

MARC

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520 |a The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8+ T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8+ effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma. 
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