CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182295 | GEO | 2022/09/01
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC8753449 | biostudies-literature
Project description:The purpose of this study is to determine whether the combination of two agents, INC280 and bevacizumab, is safe and effective when administered to patients with Glioblastoma Multiforme (GBM) who have progressed after receiving prior therapy or who have unresectable GBM.
| 2185625 | ecrin-mdr-crc
Project description:It has been previously described that in glioblastoma (GBM), BMPs deplete the tumorigenic potential of glioblastoma stem cells (GSCs), promoting their differentiation towards the astrocytic lineage. To gain more insight on how BMPs regulate differentiation in GSCs, we are interested in identifying new BMP target genes in GBM cells. To this end, the patient derived glioblastoma cell lines U3031MG and U3034MG were stimulated or not with 30ng/ml BMP7 for 2 and 24 h, total RNA was isolated from three biological replicates per condition, and a microarray screen with the Affymetrix U133plus2 platform was performed.
2021-05-01 | E-MTAB-9811 | biostudies-arrayexpress
Project description:Our study shows that after extended stimulation of human CD4+CD25+CD127- Tregs in vitro, a stable cell subset that downregulates CD27 and upregulates CD70 develops. Expanded CD27+CD70- Tregs display a gene profile which closely relates to the previously described “Treg gene signature”, whereas CD27-CD70+ Tregs express some genes associated with Treg gene signature and some genes overexpressed in conventional T cells.
2020-07-10 | GSE129251 | GEO
Project description:Glioblastoma (GBM) cells acquire mitochondria from glial cells in vitro and in vivo. This transfer is accompanied by increased tumor-initiation capacity.
2021-08-31 | GSE183004 | GEO
Project description:Recurrent glioblastoma (GBM) has a grim prognosis, though MGMT promoter methylation and IDH mutation provide a significant survival advantage. The product of IDH mutation, 2-hydroxyglutarate, increases global DNA methylation by inhibiting demethylases. While lower-grade IDH-mutant gliomas demonstrate increased methylation as a result of this process, DNA becomes relatively hypomethylated during progression from low-grade glioma to secondary (IDH-mutant) GBM. Here we show that global DNA hypomethylation also occurs during primary (IDH-wild type) GBM recurrence. Moreover, in a phase I trial of 14 patients with recurrent (IDH-wild type) GBM, we targeted DNA hypomethylation using a methyl donor treatment. In autopsied tumors from patients treated, we observed a global increase in DNA methylation compared to initial tumor. These results suggest that hypomethylation is a marker for recurrence, and its reprogramming represents a potential therapeutic vulnerability.
2021-12-31 | GSE111627 | GEO
Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Experiment Overall Design: Six Glioblastoma Multiforme patients underwent surgery. Their brain tumors were removed and analyzed via microarray. The lysate from the tumors were cultured with the patients' dendritic cells and the DCs were injected back into the patients. The patients GBMs returned and they underwent surgery a second time and those tumors were also analyzed via microarray. Tumors from the first and second GBM surgeries of 5 patients who did not receive DC vaccines are included as controls.
2009-04-11 | E-GEOD-11100 | biostudies-arrayexpress
Project description:Clostridioides difficile CD70 Genome sequencing and assembly
| PRJNA85723 | ENA
Project description:Background Despite maximal therapy with surgery, chemotherapy and radiotherapy, glioblastoma multiforme (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relate to failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multi-omics approach using transcriptomics, proteomics and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation that relates to ERBB4 signaling. A pathway tool has been developed to visualize and compare the different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxina and afatinib, that target these affected pathways. Afatinib targeting ERBB4 signaling is currently in clinical trials for GBM. Conclusions Large variation on all omics levels exist between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead a multi-omics approach can be used to identify affected pathways on the individual patient level and select potential treatment options.
2020-11-17 | PXD017952 | Pride
Project description:Background: Glioblastoma (GBM) is the most aggressive and lethal brain tumor. Although the histone deacetylase (HDAC)/Sp1 axis promotes growth and temozolomide (TMZ) resistance in glioblastoma, whether HDACs including HDAC6 are involved in modulating long non-coding RNAs (lncRNAs) to affect glioblastoma malignancy remains obscure. Methods: Integrative analysis of microarray and RNA-seq was performed to identify lncRNAs governed by HDAC6. Half-life measurement and RNA-protein pull-down assay combined with iTRAQ-based proteomic analysis were conducted to identify RNA modulators. The effect of LINC00461 on glioblastoma malignancy was evaluated using animal models and cell proliferation-related assays. Functional analysis of the LINC00461 downstream network was performed comprehensively using ingenuity pathway analysis and public databases. Results: We identified a lncRNA, LINC00461, which was substantially increased in TMZ-resistant glioblastoma cells. It was inversely correlated with the survival of mice bearing glioblastoma and was stabilized by interaction between HDAC6 and RNA-binding proteins (RBPs) such as CNOT6 and FUS. Targeting LINC00461 using MPT0B291, an HDAC6 inhibitor, decreased cell division-related proteins via the lncRNA-microRNA (miRNA)-mRNA network and caused cell cycle arrest, thereby suppressing proliferation in parental and TMZ-resistant glioblastoma cells and prolonging the survival of mice bearing glioblastoma. Conclusions: This study sheds light on the role of LINC00461 in glioblastoma malignancy and provides a novel therapeutic strategy for targeting the HDAC6/RBP/LINC00461 axis and its downstream effectors in patients with GBM.
2022-02-08 | GSE182220 | GEO