Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(8), P. 686 - 700
Published: May 7, 2022
Language: Английский
Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1654 - 1670
Published: Sept. 4, 2023
Language: Английский
Citations
29
Theranostics, Journal Year: 2023, Volume and Issue: 13(10), P. 3310 - 3329
Published: Jan. 1, 2023
Background: Glioma stem cells (GSCs) are a key factor in glioblastoma (GBM) development and treatment resistance.GSCs can be divided into the mesenchymal (MES) proneural (PN) subtypes, these two subtypes of GSCs undergo interconversion under certain conditions.MES have higher malignancy radioresistance closely associated with an immunosuppressive microenvironment.Long noncoding RNAs (lncRNAs) play broad role GBM, while subtype remains unknown.Methods: We performed RNA sequencing to explore lncRNA expression profile MES-and PN-subtype GBM tissues.The biological function host gene-MIR222HG-in was confirmed vitro vivo.Specifically, sequencing, pulldown, mass spectrometry, RIP, ChIP, luciferase reporter assays Co-IP were performed.Results: MIR222HG, which induced by SPI1, has high levels MES tissues.Functionally, we demonstrated that MIR222HG promotes transition vivo vitro.Mechanistically, bind YWHAE/HDAC5 complex promote through H4 deacetylation.Moreover, cotranscribed miR221 miR222 delivered macrophages via exosomes target SOCS3, causing polarization.Finally, PLX-4720 sensitivity is SPI1 acts on enhance radiosensitivity.Conclusions: This study demonstrates targeting block transcription cluster helps reduce combat microenvironment GBM.PLX-4720 potential drug radiosensitizer.
Language: Английский
Citations
25
Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101238 - 101238
Published: Oct. 18, 2023
Glioblastoma (GBM) is a hypoxic and "immune-cold" tumor containing rich stromal signaling molecules cell populations, such as proteases immunosuppressive tumor-associated macrophages (TAMs). Here, we seek to profile characterize the potential that may contribute GBM immunosuppression. Legumain (LGMN) emerges key protease highly enriched in TAMs transcriptionally upregulated by hypoxia-inducible factor 1-alpha (HIF1α). Functionally, increased LGMN promotes TAM polarization via activating GSK-3β-STAT3 pathway. Inhibition of macrophage HIF1α reduces polarization, impairs progression, enhances CD8+ T cell-mediated anti-tumor immunity, synergizes with anti-PD1 therapy mouse models. Thus, molecular switch connecting two hallmarks hypoxia immunosuppression, providing an actionable therapeutic intervention for this deadly disease.
Language: Английский
Citations
23
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Feb. 22, 2024
Solid tumors such as glioblastoma (GBM) exhibit hypoxic zones that are associated with poor prognosis and immunosuppression through multiple cell intrinsic mechanisms. However, release of extracellular vesicles (EVs) has the potential to transmit molecular cargos between cells. If cancer cells use EVs suppress functions macrophages under adequate oxygenation, this could be an important underlying mechanism contributing immunosuppressive immunologically cold tumor microenvironment GBM.
Language: Английский
Citations
14
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: April 29, 2024
Abstract Background Brain metastasis is one of the main causes recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy local therapy for brain metastasis, it inevitable that some cells become resistant to radiation. Microglia, as macrophages colonized brain, play an important role tumor microenvironment. Radiotherapy could activate microglia polarize into both M1 M2 phenotypes. Therefore, searching crosstalk molecules within microenvironment can specifically regulate polarization a potential strategy improving radiation resistance. Methods We used databases detect expression MIF NSCLC its relationship with prognosis. analyzed effects targeted blockade MIF/CD74 axis on function during using flow cytometry. The mouse model was assess effect growth metastasis. Result Our findings reveals macrophage migration inhibitory factor (MIF) highly expressed associated prognosis NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation promoted combination Additionally, blocking MIF-CD74 interaction between polarization. Furthermore, improved hypoxia decrease HIF-1α dependent secretion by enhanced radiosensitivity via synergistically promoting vivo. Conclusions study revealed targeting synergized
Language: Английский
Citations
11
Current Medicine, Journal Year: 2024, Volume and Issue: 3(1)
Published: April 7, 2024
Abstract Glioblastoma (GBM) is a malignant brain glioma characterized by high number of tumor-associated macrophages (TAMs) within its tissues. These TAMs have close relationship with tumor grade and prognosis. Targeting has been identified as promising therapeutic strategy. However, TAM cells play both tumor-killing tumor-promoting roles, making them double-edged sword in the immune environment. The different subtypes their effects on microenvironment remain poorly understood. This study comprehensively elucidates immunobiology glioma-associated (GAMs), including origin, classification, molecular mechanisms underlying promotion inhibition, polarization strategies, targeted therapy for GAMs current challenges perspectives modulation. Further research macrophage function mechanism may provide new immunological basis treating GBM patients enhancing efficacy immunotherapy.
Language: Английский
Citations
9
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: May 8, 2024
Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member microenvironment (TME), widely distributed in circulation. Recently, discovery cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into origins neutrophils CNS. Neutrophils brain may originate more from skull adjacent vertebral bone marrow. They cross blood-brain barrier (BBB) under action chemokines enter parenchyma, subsequently migrating to glioma TME undergoing phenotypic changes upon contact with cells. Under glycolytic metabolism model, show complex dual functions different stages cancer progression, including participation immune suppression, anti-tumor effects gliomas. Additionally, interact other cells, playing crucial role immunotherapy. Targeting be novel generation immunotherapy improve efficacy treatments. This article reviews molecular mechanisms infiltrating external environment, detailing origin, functions, classifications, targeted therapies context glioma.
Language: Английский
Citations
9
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)
Published: March 13, 2024
Abstract In recent years, several studies described the close relationship between composition of gut microbiota and brain functions, highlighting importance gut-derived metabolites in mediating neuronal glial cells cross-talk physiological pathological condition. Gut dysbiosis may affects cerebral tumors growth progression, but specific involved this modulation have not been identified yet. Using a syngeneic mouse model glioma, we investigated role induced by administration non-absorbable antibiotics on metabolome tumor microenvironment. We report that treatment induced: (1) alteration profiles; (2) modeling microenvironment toward pro-angiogenic phenotype which microglia glioma are actively involved; (3) increased stemness; (4) trans-differentiation into endothelial precursor cells, thus increasing vasculogenesis. propose glycine as metabolite that, ABX-induced dysbiosis, shapes contributes to progression.
Language: Английский
Citations
8
Cancer Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 7, 2025
Glioblastoma (GBM) involves disruptions in the blood-brain barrier (BBB) and alterations immune microenvironment, including activation of glioma-associated macrophages (GAMs). Vascular endothelial growth factor inhibitors, commonly used recurrent GBM treatment, can influence these processes. This study investigates relationship between BBB disruption GAM activation, focusing on plasmalemma vesicle-associated protein (PLVAP), a marker disruption, α1-acid glycoprotein (AGP), an inflammatory implicated tumor progression. PLVAP expression was analyzed by immunohistochemistry (IHC) human samples to determine correlations with grade, proliferation, activation. Pre- post-bevacizumab treatment were compared assess changes integrity macrophage activity. AGP's role studied through vitro assays glioma implantation AGP knockout mice, assessments angiogenesis. Results showed elevated higher-grade gliomas, correlating increased proliferation particularly around PLVAP-positive vessels. Bevacizumab reduced localized regions promoting macrophage-mediated vitro. mice demonstrated angiogenesis prolonged survival. Spatial analysis revealed macrophage-inducing molecules near These findings suggest as malignancy. AGP, associated leakage, contributes progression, highlighting its potential therapeutic target for GBM.
Language: Английский
Citations
1
Trends in cancer, Journal Year: 2022, Volume and Issue: 8(10), P. 839 - 854
Published: May 24, 2022
Language: Английский
Citations
37