ArticleInternational journal of molecular sciences2021
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.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.Cancer metastasis reviews · 2026Review
- M2 macrophage infiltration associated with CXCL8 predicts grade 4 prognosis and differentiates glioma grades.Discover oncology · 2025Article
- New experimental therapies for glioblastoma: a review of preclinical research.Acta neuropathologica communications · 2025Review
- Nano-Based Technology in Glioblastoma.Molecules (Basel, Switzerland) · 2025Review
- Chemoradiation-Altered Micromilieu of Glioblastoma Cells Particularly Impacts M1-like Macrophage Activation.International journal of molecular sciences · 2025Article
- Prognostic and predictive determinants in high-grade gliomas: integrating tumor-intrinsic biology with patient and system-level factors.Frontiers in neurology · 2025Review
- Advances in tumor-associated macrophage-mediated chemotherapeutic resistance in glioma.Frontiers in cell and developmental biology · 2025Review
- Unveiling the Inflammatory Landscape of Recurrent Glioblastoma through Histological-Based Assessments.Cancers · 2024Review
- Exosomes as drug delivery systems in glioma immunotherapy.Journal of nanobiotechnology · 2024Review
- New insights into targeted therapy of glioblastoma using smart nanoparticles.Cancer cell international · 2024Review
- MET receptor serves as a promising target in melanoma brain metastases.Acta neuropathologica · 2024Article
- CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment.International journal of molecular sciences · 2023Article
- Combined Inhibition of Indolamine-2,3-Dioxygenase 1 and C-X-C Chemokine Receptor Type 2 Exerts Antitumor Effects in a Preclinical Model of Cervical Cancer.Biomedicines · 2023Article
- Mapping high-grade glioma immune infiltration to 5-ALA fluorescence levels: TCGA data computation, classical histology, and digital image analysis.Journal of neuro-oncology · 2023Article
- Macrophage's role in solid tumors: two edges of a sword.Cancer cell international · 2023Article
- Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment.Neurology international · 2023Review
- Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma.Cell death & disease · 2023Review
- ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma.Journal of neuroinflammation · 2022Review
- Combining TMZ and SB225002 induces changes of CXCR2 and VEGFR signalling in primary human endothelial cellsOncology reports · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.