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

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

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Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 20, 2024

Abstract Glioblastoma is one of the most lethal cancers with current therapeutic options lacking major successes. This underlines necessity to understand glioblastoma biology on other levels and use these learnings for development new concepts. Mounting evidence in field circadian medicine points a tight interplay between disturbances system progression. The clock, an internal biological mechanism governing numerous physiological processes across 24-h cycle, also plays pivotal role regulationg key cellular functions, including DNA repair, cell cycle progression, apoptosis. These are integral tumour response therapy. Disruptions rhythms can influence growth, invasion, treatment patients. In this review, we explore robust association cancer hallmarks within context glioblastoma. We further discuss impact clock eight shown previously link molecular different cancers, summarize putative proteins rhythm chronotherapy By unravelling mechanisms behind intricate connections researchers pave way identification potential targets, innovative strategies personalized approaches. conclusion, review underscores significant advancement understanding future therapies glioblastoma, ultimately leading enhanced outcomes

Language: Английский

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Muscone restores anoikis sensitivity in TMZ-resistant glioblastoma cells by suppressing TOP2A via the EGFR/Integrin β1/FAK signaling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155714 - 155714

Published: May 5, 2024

Language: Английский

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Temozolomide chemotherapy for patients with newly diagnosed glioblastoma in the CENTRIC EORTC 26071-22072 and CORE trials: does time of administration matter?

Neuro-Oncology Practice, Journal Year: 2025, Volume and Issue: 12(2), P. 291 - 300

Published: Jan. 13, 2025

Preclinical work and retrospective studies suggest that temozolomide chemotherapy in glioblastoma may be more effective when administered the morning rather than evening. Here we examine effect of timing a large cohort patients 2 contemporaneous randomized clinical trials. We assessed toxicity survival data with newly diagnosed enrolled CENTRIC EORTC 26071-22072 (n = 545, MGMT methylated) CORE 265, unmethylated) compared outcome who took maintenance (adjuvant) (TMZ) either (TMZ-m), afternoon (TMZ-a) or evening (TMZ-e). In CORE, n 102/260 (39%) 50/198 (25%) received TMZ versus 35/260 (13%) 34/198 (17%) There was no difference overall (OS) between TMZ-m TMZ-e groups (CENTRIC: adjusted mOS 20.6 months (95% confidence interval [CI], 18.4-23.4) vs 21.1 CI, 18.4-24.5) TMZ-e; hazard ratio (HR), 0.93 0.63-1.39); P .7; CORE: mOS, 10.9 (95%CI, 9.7-11.8) 11.4 9.9-12.9) HR, 0.87, 95%CI, 0.55-1.38); .6). The group had higher proportion bone marrow 33% 11%, .013, 24% 3%, < .01). this post hoc analysis, found based on time administration. Bone might occur frequently is morning. Given limitation to from deceased only, these analyses should viewed as exploratory only.

Language: Английский

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Ultrasound-responsive nanoparticles for imaging and therapy of brain tumors

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101661 - 101661

Published: March 1, 2025

Language: Английский

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Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Circulation Research, Journal Year: 2024, Volume and Issue: 134(6), P. 727 - 747

Published: March 14, 2024

The blood-brain barrier (BBB) is a critical interface separating the central nervous system from peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled profound connection between BBB circadian rhythms, endogenous oscillations synchronizing biological processes with 24-hour light-dark cycle. This review explores significance of rhythms in context functions, an emphasis on substrate passage through BBB. Our discussion includes efflux transporters molecular timing mechanisms that regulate their activities. A significant focus this potential implications chronotherapy, leveraging our knowledge for improving drug delivery to brain. Understanding temporal changes can lead optimized administration, enhance therapeutic efficacy neurological disorders while reducing side effects. By elucidating interplay transport across BBB, offers insights into innovative interventions.

Language: Английский

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Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this controlled by clock genes, which function to harmoniously express molecular levels facilitate orderly coordination various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation immunity. root cause tumorigenesis body loses its normal growth at genetic level. Long-term disruptions circadian rhythms caused factors shift work, jet lag, unstable sleep patterns can impact health, leading health problems, including cancer. controls most functions related cancer progression, has significant on ability immune cells detect promote their clearance crucial implication for future tumor immunotherapy. This article aims review crosstalk between dysregulation tumorigenesis, response. Additionally, we discuss role disruption therapy, highlighting potential optimize treatment timing improve therapeutic outcomes.

Language: Английский

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Implantable systems for neurological chronotherapy

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115574 - 115574

Published: April 1, 2025

Language: Английский

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Nose-to-brain delivery of sorafenib-loaded lipid-based poloxamer-carrageenan nanoemulgel: Formulation and therapeutic investigation in glioblastoma-induced orthotopic rat model

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142861 - 142861

Published: April 1, 2025

Language: Английский

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Circadian Rhythm Disruption in Triple‐Negative Breast Cancer: Molecular Insights and Treatment Strategies

Journal of Pineal Research, Journal Year: 2025, Volume and Issue: 77(3)

Published: April 1, 2025

ABSTRACT Disruption of the circadian clock has been closely linked to initiation, development, and progression cancer. This study aims explore impact rhythm disruption (CRD) on triple‐negative breast cancer (TNBC). We analyzed bulk single‐cell RNA sequencing data assess status in TNBC using multiple bioinformatic tools, alongside metabolomic profiles tumor microenvironment evaluations understand influence CRD metabolic reprogramming immune evasion. The results indicate that experiences profound CRD. Patients with a higher CRDscore exhibit significantly poorer relapse‐free survival compared those lower CRDscore. Cyclic ordering by periodic structure (CYCLOPS) identified significant changes rhythmic gene expression patterns between normal tissues, showing “rush hour” effect, where peak times are concentrated within specific time windows. Transcripts disrupted rhythms were found be involved key pathways related cell cycle regulation, metabolism, response. Metabolomic analysis further revealed TNBCs high enriched carbohydrate amino acid metabolism pathways, notably upregulation tryptophan metabolism. High was also an immunosuppressive microenvironment, characterized reduced infiltration, exhausted CD8 + T cells, diminished response checkpoint blockade therapy. These findings suggest molecular may activate thereby promoting evasion potentially reducing effectiveness immunotherapy.

Language: Английский

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