The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(1), P. 26 - 41

Published: Oct. 10, 2019

Language: Английский

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Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions

Neuro-Oncology, Journal Year: 2020, Volume and Issue: 22(8), P. 1073 - 1113

Published: April 20, 2020

Abstract Glioblastomas are the most common form of malignant primary brain tumor and an important cause morbidity mortality. In recent years there have been advances in understanding molecular pathogenesis biology these tumors, but this has not translated into significantly improved outcomes for patients. consensus review from Society Neuro-Oncology (SNO) European Association (EANO), current management isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. addition, novel therapies such as targeted therapies, agents targeting DNA damage response metabolism, immunotherapies, viral reviewed, well challenges future directions research.

Language: Английский

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Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 9, 2022

Abstract A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and molecular heterogeneity immune infiltrates gliomas. Here, we report an integrated analysis 201,986 human glioma, immune, other stromal cells at single cell level. In doing so, discover extensive spatial infiltrates. We identify signatures nine distinct myeloid subtypes, which five are independent prognostic indicators glioma patient survival. Furthermore, S100A4 as a regulator suppressive T demonstrate that deleting S100a4 non-cancer sufficient to reprogram landscape significantly improve This study provides insights into spatial, molecular, functional glioma-associated demonstrates utility this dataset discovering therapeutic targets poorly immunogenic cancer.

Language: Английский

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Engineering Macrophage Exosome Disguised Biodegradable Nanoplatform for Enhanced Sonodynamic Therapy of Glioblastoma

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(15)

Published: Feb. 8, 2022

Sonodynamic therapy (SDT) exhibits high tissue penetration and negligible radiation damage to normal tissues, thus emerges as a promising cancer therapeutic modality for glioblastoma (GBM). However, the blood-brain barrier (BBB) hypoxic microenvironment greatly limit SDT efficiency. In this work, biodegradable nanoplatform (termed CSI) is fabricated by encapsulating catalase (CAT) into silica nanoparticles (CAT@SiO2 ) tumor hypoxia relief, then loaded with sonosensitizer indocyanine green (ICG). Inspired ability of macrophages cross BBB, CSI further coated AS1411 aptamer-modified macrophage exosomes form CSI@Ex-A, which possesses efficient BBB good cancer-cell-targeting capability. After cell endocytosis, highly expressed glutathione (GSH) triggeres biodegradation released CAT catalyzes hydrogen peroxide (H2 O2 produce relieve hypoxia. The GSH depletion self-supplying effectively enhances efficiency both in vitro vivo. addition, resulting CSI@Ex-A biocompatibility long circulation time. These findings demonstrate that may serve competent GBM therapy, potential clinical translation.

Language: Английский

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Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection

Nature Nanotechnology, Journal Year: 2021, Volume and Issue: 16(5), P. 538 - 548

Published: Feb. 1, 2021

Language: Английский

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EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 14, 2022

Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in pathophysiological processes TME remodelling various tumours.CircRNA sequencing analysis was performed explore circRNA expression profiles normal glioma tissues. The biological function novel circRNA, namely, circNEIL3, development confirmed both vitro vivo. Mechanistically, RNA pull-down, mass spectrum, immunoprecipitation (RIP), luciferase reporter, co-immunoprecipitation assays were conducted.We identified which could be cyclized EWS RNA-binding protein 1(EWSR1), upregulated tissues correlate positively progression. Functionally, we that circNEIL3 promotes tumorigenesis carcinogenic progression stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding 3) protein, known oncogenic preventing HECTD4-mediated ubiquitination. Moreover, overexpression cells drives macrophage infiltration into (TME). Finally, is packaged exosomes hnRNPA2B1 transmitted infiltrated associated macrophages (TAMs), enabling them acquire properties stabilizing turn promoting progression.This work reveals plays nonnegligible multifaceted gliomagenesis, tumour-promoting phenotypes polarization, highlighting potential prognostic biomarker therapeutic target glioma.

Language: Английский

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Intracavity generation of glioma stem cell–specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(656)

Published: Aug. 3, 2022

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating GSCs is critical for preventing postoperative this devastating disease, yet effective strategies remain elusive. Here, we report cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding cavity prevent relapse. Specifically, demonstrate CAR gene–laden nanoporter in hydrogel can introduce GSC-targeted genes into MΦ nuclei intracavity delivery generate CAR-MΦs mouse models GBM. These were able seek engulf clear by stimulating an adaptive antitumor immune response tumor microenvironment prevented inducing long-term immunity mice. In orthotopic patient–derived glioblastoma humanized model, combined treatment CD47 antibody increased frequency positive responding suppressed negative regulating cells, conferring robust tumoricidal postsurgical inhibiting Therefore, our work establishes locoregional strategy priming cancer cell–specific broad application suffering from recurrent malignancies.

Language: Английский

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Immunotherapy for glioblastoma: the promise of combination strategies

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Jan. 25, 2022

Glioblastoma (GBM) treatment has remained almost unchanged for more than 20 years. The current standard of care involves surgical resection (if possible) followed by concomitant radiotherapy and chemotherapy. In recent years, immunotherapy strategies have revolutionized the many cancers, increasing hope GBM therapy. However, mostly due to high, multifactorial immunosuppression occurring in microenvironment, poor knowledge neuroimmune system presence blood-brain barrier, efficacy is still low. Recently, new treatments employed combinations provided encouraging results both preclinical clinical studies. lessons learned from trials highlight importance tackling different arms immunity. this review, we aim summarize evidence regarding combination terms immune survival benefits management. outcomes studies assessing classes immunotherapeutic agents (e.g., checkpoint blockade vaccines) will be discussed. Finally, future ameliorate facilitate translation address unmet medical needs GBM.

Language: Английский

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Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(17)

Published: May 4, 2022

Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis a newly discovered method programmed cell death opens new direction for GBM treatment. However, poor blood-brain barrier (BBB) penetration, reduced tumor targeting ability, potential compensatory mechanisms hinder effectiveness ferroptosis agents during Here, novel composite therapeutic platform combining magnetic features drug delivery properties nanoparticles with BBB penetration abilities siRNA encapsulation engineered exosomes therapy presented. This can be enriched in brain under local localization angiopep-2 peptide-modified trigger transcytosis, allowing particles to cross target cells by recognizing LRP-1 receptor. Synergistic achieved combined triple actions disintegration dihydroorotate dehydrogenase glutathione peroxidase 4 defense axis Fe

Language: Английский

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Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape

Cancer Immunology Immunotherapy, Journal Year: 2021, Volume and Issue: 70(7), P. 2035 - 2048

Published: Jan. 9, 2021

Language: Английский

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