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

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作者
Lorraine Weidner
Julia Lorenz
Stefanie Quach
Frank K. Braun
Tanja Rothhammer-Hampl
Laura-Marie Ammer
Arabel Vollmann-Zwerenz
Laura M. Bartos
Franziska J. Dekorsy
Adrien Holzgreve
Sabrina V. Kirchleitner
Niklas Thon
Tobias Greve
Viktoria Ruf
Jochen Herms
Stefanie Bader
Vladimir M. Milenkovic
Louisa von Baumgarten
Ayse N. Menevse
Abir Hussein
Julian Sax
Christian H. Wetzel
Rainer Rupprecht
Martin Proescholdt
Nils O. Schmidt
Philipp Beckhove
Peter Hau
Joerg-Christian Tonn
Peter Bartenstein
Matthias Brendel
Nathalie L. Albert
Markus J. Riemenschneider
机构
[1] Regensburg University Hospital,Department of Neuropathology
[2] Regensburg University Hospital,Wilhelm Sander Neuro
[3] University Hospital of Munich,Oncology Unit
[4] LMU Munich,Department of Neurosurgery
[5] Regensburg University Hospital,Department of Neurology
[6] University Hospital of Munich,Department of Nuclear Medicine
[7] LMU Munich,Center for Neuropathology and Prion Research
[8] LMU Munich,Department of Psychiatry and Psychotherapy
[9] University Regensburg,Division of Interventional Immunology
[10] Leibniz Institute for Immunotherapy,Department of Neurosurgery
[11] University Hospital Regensburg,Department of Internal Medicine III
[12] University Hospital Regensburg,undefined
[13] German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy),undefined
关键词
TSPO; Glioma; PET; Imaging; Promotor methylation; RNA seq; Immunohistochemistry; Intratumoral heterogeneity; Microglia; Myeloid cells;
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摘要
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.
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