Proteomic profiling of IDH-wildtype Glioblastoma Tissue and Serum uncovers prognostic Subtypes and Marker Candidates DOI Open Access
Tilman Werner,

Agnes Schäfer,

Michael Hennes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Background IDH-wildtype glioblastoma (GBM) is the most prevalent primary brain cancer with a 5-year survival rate below 10%. Despite combined treatment through extensive resection and radiochemotherapy, nine out of ten patients develop recurrences. The lack targeted options reliable diagnostic markers for recurrent tumors remain major challenges. Methods & Aims In this study, we present proteomic characterization tissue serum from 55 initial GBM five matching recurrences, which investigated tumor subtypes signatures associated recurrence. Results Primary revealed four distinct subgroups hierarchical clustering: neuronal cluster elevated mature neuron markers, an innate immunity increased protease expression, mixed cluster, stem-cell cluster. Neurodevelopmental inflammatory processes were identified as key factors influencing clustering, proteolytic activity increasing relative to degree inflammation. An analysis comprising proteins lower coverage confirmed expanded pattern. Patients in exhibited significantly longer compared those patient-matched differential expression analysis, displayed altered protein their counterparts, emphasizing plasticity tumors. Investigation proteomes before after surgery, using depletion-based protocol, highly patient-specific stable proteome compositions, despite notable increase inflammation post-surgery. However, levels circulating products matched within one fragment proteolysis activated receptor 2 (PAR2) consistently dropped abundance removal inflamed Conclusion Overall, describe large cohort. We subgroups, molecular patterns recurrence, bloodstream, may improve risk prediction GBM.

Language: Английский

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives DOI Creative Commons

Hao Lin,

Chaxian Liu,

An-Kang Hu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Language: Английский

Citations

60
Hypoxia-induced complement component 3 promotes aggressive tumor growth in the glioblastoma microenvironment DOI Creative Commons
Rebecca Rosberg, Karolina I. Smoląg, Jonas Sjölund

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(19)

Published: Aug. 22, 2024

Glioblastoma (GBM) is the most aggressive form of glioma with a high rate relapse despite intensive treatment. Tumor recurrence tightly linked to radio-resistance, which in turn associated hypoxia. Here, we discovered strong link between hypoxia and local complement signaling using publicly available bulk, single-cell, spatially resolved transcriptomic data from patients GBM. Complement component 3 (C3) receptor C3AR1 were both disease shorter survival human glioma. In genetically engineered mouse model GBM, found C3 specifically hypoxic tumor areas. vitro, an oxygen level-dependent increase expression response several GBM stromal cell types. C3a induced M2 polarization cultured microglia macrophages C3aR-dependent fashion. Targeting C3aR antagonist SB290157 prolonged glioma-bearing mice alone combination radiotherapy while reducing number M2-polarized macrophages. Our findings establish pathways support role hypoxia-induced C3a/C3aR as contributor aggressiveness by regulating macrophage polarization.

Language: Английский

Citations

5
A novel role of exostosin glycosyltransferase 2 (EXT2) in glioblastoma cell metabolism, radiosensitivity and ferroptosis DOI Creative Commons

Rocío Matesanz-Sánchez,

Mirko Peitzsch,

Inga Lange

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

Citations

0
Roles of extracellular vesicles in glioblastoma: foes, friends and informers DOI Creative Commons
Taral R. Lunavat, Lisa Nieland,

Anne B. Vrijmoet

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 24, 2023

Glioblastoma (GB) tumors are one of the most insidious cancers which take over brain and defy therapy. Over time in response to treatment tumor cells microenvironment (TME) undergo many genetic/epigenetic driven changes their phenotypes this is reflected cellular contents within extracellular vesicles (EVs) they produce. With result that some EVs try subdue (friends brain), while others participate glioblastoma takeover (foes brain) a dynamic ever changing process. Monitoring these biofluids can inform decisions based on GB status guide therapeutic intervention. This review covers primarily recent research describing different cell types brain, as well cells, EV deluge. includes produced by manipulate transcriptome normal environment support growth (foes), responses restrict invasion, including traveling cervical lymph nodes present neo-antigens dendritic (DCs). In addition released into report living via cargo thus serving biomarkers. However, influence major factor immune suppression coercion join “band wagon”. Efforts being made deploy vehicles for drugs small inhibitory RNAs. Increasing knowledge about TME utilized track progression therapy even weaponize fight tumor.

Language: Английский

Citations

6
Hypoxia-induced Complement Component 3 Promotes Aggressive Tumor Growth in the Glioblastoma Microenvironment DOI Creative Commons
Rebecca Rosberg, Karolina I. Smoląg, Jonas Sjölund

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 29, 2024

Abstract Glioblastoma (GBM) is the most aggressive form of glioma with a high rate relapse despite intensive treatment. Tumor recurrence tightly linked to radio-resistance, which in turn associated hypoxia. Here, we discovered strong link between hypoxia and local complement signaling using publicly available bulk, single cell, spatially resolved transcriptomic data from human GBM patients. Complement component 3 ( C3 ) receptor C3AR1 were both disease shorter survival glioma. In genetically engineered mouse model GBM, found specifically hypoxic tumor areas. vitro, an oxygen level-dependent increase expression response several stromal cell types. Presence increased proliferation cells under conditions, as well clonal following radiation. Targeting C3aR antagonist SB290157 decreased self-renewal prolonged bearing mice alone combination radiotherapy while reducing number M2-polarized macrophages. Our findings establish pathways support role hypoxia-induced C3a-C3aR contributor aggressiveness.

Language: Английский

Citations

0
Proteomic profiling of IDH-wildtype Glioblastoma Tissue and Serum uncovers prognostic Subtypes and Marker Candidates DOI Open Access
Tilman Werner,

Agnes Schäfer,

Michael Hennes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Background IDH-wildtype glioblastoma (GBM) is the most prevalent primary brain cancer with a 5-year survival rate below 10%. Despite combined treatment through extensive resection and radiochemotherapy, nine out of ten patients develop recurrences. The lack targeted options reliable diagnostic markers for recurrent tumors remain major challenges. Methods & Aims In this study, we present proteomic characterization tissue serum from 55 initial GBM five matching recurrences, which investigated tumor subtypes signatures associated recurrence. Results Primary revealed four distinct subgroups hierarchical clustering: neuronal cluster elevated mature neuron markers, an innate immunity increased protease expression, mixed cluster, stem-cell cluster. Neurodevelopmental inflammatory processes were identified as key factors influencing clustering, proteolytic activity increasing relative to degree inflammation. An analysis comprising proteins lower coverage confirmed expanded pattern. Patients in exhibited significantly longer compared those patient-matched differential expression analysis, displayed altered protein their counterparts, emphasizing plasticity tumors. Investigation proteomes before after surgery, using depletion-based protocol, highly patient-specific stable proteome compositions, despite notable increase inflammation post-surgery. However, levels circulating products matched within one fragment proteolysis activated receptor 2 (PAR2) consistently dropped abundance removal inflamed Conclusion Overall, describe large cohort. We subgroups, molecular patterns recurrence, bloodstream, may improve risk prediction GBM.

Language: Английский

Citations

0