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Bartos, L.M.* ; Quach, S.* ; Zenatti, V.* ; Kirchleitner, S.V.* ; Blobner, J.* ; Wind-Mark, K.* ; Kolabas, Z.I. ; Ulukaya, S. ; Holzgreve, A.* ; Ruf, V.C.* ; Kunze, L.H.* ; Kunte, S.T.* ; Hoermann, L.* ; Härtel, M.* ; Park, H.E.* ; Groß, M.* ; Franzmeier, N.* ; Zatcepin, A.* ; Zounek, A.* ; Kaiser, L.* ; Riemenschneider, M.J.* ; Perneczky, R.* ; Rauchmann, B.S.* ; Stöcklein, S.* ; Ziegler, S.* ; Herms, J.* ; Ertürk, A. ; Tonn, J.C.* ; Thon, N.* ; von Baumgarten, L.* ; Prestel, M.* ; Tahirovic, S.* ; Albert, N.L.* ; Brendel, M.*

Remote neuroinflammation in newly diagnosed glioblastoma correlates with unfavorable clinical outcome.

Clin. Cancer Res. 30, 4618-4634 (2024)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
PURPOSE: Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in the brain of patients with glioblastoma have been described. However, the impact and molecular signature of neuroinflammation distant of the primary tumor site have not yet been thoroughly elucidated. EXPERIMENTAL DESIGN: We performed translocator protein (TSPO)-PET in patients with newly diagnosed glioblastoma (n = 41), astrocytoma WHO grade 2 (n = 7), and healthy controls (n = 20) and compared TSPO-PET signals of the non-lesion (i.e., contralateral) hemisphere. Back-translation into syngeneic SB28 glioblastoma mice was used to characterize Pet alterations on a cellular level. Ultimately, multiplex gene expression analyses served to profile immune cells in remote brain. RESULTS: Our study revealed elevated TSPO-PET signals in contralateral hemispheres of patients with newly diagnosed glioblastoma compared to healthy controls. Contralateral TSPO was associated with persisting epileptic seizures and shorter overall survival independent of the tumor phenotype. Back-translation into syngeneic glioblastoma mice pinpointed myeloid cells as the predominant source of contralateral TSPO-PET signal increases and identified a complex immune signature characterized by myeloid cell activation and immunosuppression in distant brain regions. CONCLUSIONS: Neuroinflammation within the contralateral hemisphere can be detected with TSPO-PET imaging and associates with poor outcome in patients with newly diagnosed glioblastoma. The molecular signature of remote neuroinflammation promotes the evaluation of immunomodulatory strategies in patients with detrimental whole brain inflammation as reflected by high TSPO expression.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Regulatory T-cells; Radioligand Binding; Pet; Expression; Macrophages; Disease; Gliomas; Marker; Growth; Cd74
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Journal Clinical Cancer Research
Quellenangaben Volume: 30, Issue: 20, Pages: 4618-4634 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Grants Bavarian Cancer Research Center (BZKF)
Else Kroener-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy
Verein zur Foerderung von Wissenschaft und Forschung an der Medizinischen Fakultaet der LMU Muenchen (WiFoMed)
Friedrich-Baur-Stiftung
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)