TY  - JOUR
AU  - Bartos, Laura M
AU  - Quach, Stefanie
AU  - Zenatti, Valerio
AU  - Kirchleitner, Sabrina V
AU  - Blobner, Jens
AU  - Wind, Karin
AU  - Kolabas, Zeynep Ilgin
AU  - Ulukaya, Selin
AU  - Holzgreve, Adrien
AU  - Ruf, Viktoria C
AU  - Kunze, Lea
AU  - Kunte, Sebastian T
AU  - Hoermann, Leonie
AU  - Härtel, Marlies
AU  - Park, Ha Eun
AU  - Groß, Mattes
AU  - Franzmeier, Nicolai
AU  - Zatcepin, Artem
AU  - Zounek, Adrian
AU  - Kaiser, Lena
AU  - Riemenschneider, Markus J
AU  - Perneczky, Robert
AU  - Rauchmann, Boris Stephan
AU  - Stöcklein, Sophia
AU  - Ziegler, Sibylle
AU  - Herms, Jochen
AU  - Ertürk, Ali
AU  - Tonn, Joerg C
AU  - Thon, Niklas
AU  - von Baumgarten, Louisa
AU  - Prestel, Matthias
AU  - Tahirovic, Sabina
AU  - Albert, Nathalie L
AU  - Brendel, Matthias
TI  - Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome.
JO  - Clinical cancer research
VL  - 30
IS  - 20
SN  - 1078-0432
CY  - Philadelphia, Pa. [u.a.]
PB  - AACR
M1  - DZNE-2024-01226
SP  - 4618 - 4634
PY  - 2024
AB  - 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.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.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.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.
KW  - Glioblastoma: pathology
KW  - Glioblastoma: genetics
KW  - Glioblastoma: metabolism
KW  - Glioblastoma: diagnosis
KW  - Glioblastoma: mortality
KW  - Humans
KW  - Animals
KW  - Mice
KW  - Receptors, GABA: metabolism
KW  - Receptors, GABA: genetics
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Brain Neoplasms: pathology
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: metabolism
KW  - Brain Neoplasms: diagnosis
KW  - Neuroinflammatory Diseases: pathology
KW  - Neuroinflammatory Diseases: etiology
KW  - Neuroinflammatory Diseases: diagnosis
KW  - Adult
KW  - Positron-Emission Tomography: methods
KW  - Aged
KW  - Prognosis
KW  - Tumor Microenvironment: immunology
KW  - Disease Models, Animal
KW  - Receptors, GABA (NLM Chemicals)
KW  - TSPO protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39150564
C2  - pmc:PMC11474166
DO  - DOI:10.1158/1078-0432.CCR-24-1563
UR  - https://pub.dzne.de/record/272724
ER  -