Weidner, Lorraine and Lorenz, Julia and Quach, Stefanie and Braun, Frank K. and Rothhammer-Hampl, Tanja and Ammer, Laura-Marie and Vollmann-Zwerenz, Arabel and Bartos, Laura M. and Dekorsy, Franziska J. and Holzgreve, Adrien and Kirchleitner, Sabrina V. and Thon, Niklas and Greve, Tobias and Ruf, Viktoria and Herms, Jochen and Bader, Stefanie and Milenkovic, Vladimir M. and von Baumgarten, Louisa and Menevse, Ayse N. and Hussein, Abir and Sax, Julian and Wetzel, Christian H. and Rupprecht, Rainer and Proescholdt, Martin and Schmidt, Nils O. and Beckhove, Philipp and Hau, Peter and Tonn, Joerg-Christian and Bartenstein, Peter and Brendel, Matthias and Albert, Nathalie L. and Riemenschneider, Markus J. (2023) Translocator protein (18kDA) (TSPO) marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 11 (1): 147. ISSN 2051-5960,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; MICROENVIRONMENT; EXPRESSION; CANCER; PROGRESSION; SUBTYPES; REVEALS; CLASSIFICATION; IDENTIFICATION; PROMOTER; TSPO; Glioma; PET; Imaging; Promotor methylation; RNA seq; Immunohistochemistry; Intratumoral heterogeneity; Microglia; Myeloid cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie Medicine > Abteilung für Neuropathologie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 15:17 |
| Last Modified: | 08 Mar 2024 15:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59216 |
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