Translocator protein (18kDA) (TSPO) marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages.

Autor: Weidner L; Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany., Lorenz J; Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany., Quach S; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Braun FK; Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany., Rothhammer-Hampl T; Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany., Ammer LM; Department of Neurology, Regensburg University Hospital, Regensburg, Germany., Vollmann-Zwerenz A; Department of Neurology, Regensburg University Hospital, Regensburg, Germany., Bartos LM; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Dekorsy FJ; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Holzgreve A; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Kirchleitner SV; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Thon N; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Greve T; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Ruf V; Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany., Herms J; Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany., Bader S; Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany., Milenkovic VM; Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany., von Baumgarten L; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Menevse AN; Division of Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Germany., Hussein A; Division of Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Germany., Sax J; Division of Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Germany., Wetzel CH; Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany., Rupprecht R; Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany., Proescholdt M; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany.; Department of Neurosurgery, University Hospital Regensburg, 93053, Regensburg, Germany., Schmidt NO; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany.; Department of Neurosurgery, University Hospital Regensburg, 93053, Regensburg, Germany., Beckhove P; Division of Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Germany.; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Hau P; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany.; Department of Neurology, Regensburg University Hospital, Regensburg, Germany., Tonn JC; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Bartenstein P; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Brendel M; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Albert NL; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Riemenschneider MJ; Department of Neuropathology, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. markus.riemenschneider@ukr.de.; Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany. markus.riemenschneider@ukr.de.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2023 Sep 11; Vol. 11 (1), pp. 147. Date of Electronic Publication: 2023 Sep 11.
DOI: 10.1186/s40478-023-01651-5
Abstrakt: TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing.We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages.In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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