dc.contributor.author
Urbantat, Ruth M.
dc.contributor.author
Jelgersma, Claudius
dc.contributor.author
Brandenburg, Susan
dc.contributor.author
Nieminen-Kelhä, Melina
dc.contributor.author
Kremenetskaia, Irina
dc.contributor.author
Zollfrank, Julia
dc.contributor.author
Mueller, Susanne
dc.contributor.author
Rubarth, Kerstin
dc.contributor.author
Koch, Arend
dc.contributor.author
Vajkoczy, Peter
dc.contributor.author
Acker, Gueliz
dc.date.accessioned
2022-01-28T12:58:44Z
dc.date.available
2022-01-28T12:58:44Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/33795
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-33515
dc.description.abstract
Tumor recurrence is the main challenge in glioblastoma (GBM) treatment. Gold standard therapy temozolomide (TMZ) is known to induce upregulation of IL8/CXCL2/CXCR2 signaling that promotes tumor progression and angiogenesis. Our aim was to verify the alterations on this signaling pathway in human GBM recurrence and to investigate the impact of TMZ in particular. Furthermore, a combi-therapy of TMZ and CXCR2 antagonization was established to assess the efficacy and tolerability. First, we analyzed 76 matched primary and recurrent GBM samples with regard to various histological aspects with a focus on the role of TMZ treatment and the assessment of predictors of overall survival (OS). Second, the combi-therapy with TMZ and CXCR2-antagonization was evaluated in a syngeneic mouse tumor model with in-depth immunohistological investigations and subsequent gene expression analyses. We observed a significantly decreased infiltration of tumor-associated microglia/macrophages (TAM) in recurrent tumors, while a high TAM infiltration in primary tumors was associated with a reduced OS. Additionally, more patients expressed IL8 in recurrent tumors and TMZ therapy maintained CXCL2 expression. In mice, enhanced anti-tumoral effects were observed after combi-therapy. In conclusion, high TAM infiltration predicts a survival disadvantage, supporting findings of the tumor-promoting phenotype of TAMs. Furthermore, the combination therapy seemed to be promising to overcome CXCR2-mediated resistance.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
glioblastoma
en
dc.subject
antiangiogenic therapy
en
dc.subject
combination therapy
en
dc.subject
temozolomide
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
11180
dcterms.bibliographicCitation.doi
10.3390/ijms222011180
dcterms.bibliographicCitation.journaltitle
International Journal of Molecular Sciences
dcterms.bibliographicCitation.number
20
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
22
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34681839
dcterms.isPartOf.eissn
1422-0067