Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Cell, Journal Year: 2020, Volume and Issue: 181(7), P. 1643 - 1660.e17

Published: May 28, 2020

Language: Английский

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Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients

Genomics Proteomics & Bioinformatics, Journal Year: 2021, Volume and Issue: 19(1), P. 1 - 12

Published: Feb. 1, 2021

Gliomas are the most common and malignant intracranial tumors in adults. Recent studies have revealed significance of functional genomics for glioma pathophysiological treatments. However, access to comprehensive genomic data analytical platforms is often limited. Here, we developed Chinese Glioma Genome Atlas (CGGA), a user-friendly portal storage interactive exploration cross-omics data, including nearly 2000 primary recurrent samples from cohort. Currently, open provided whole-exome sequencing (286 samples), mRNA (1018 samples) microarray (301 DNA methylation (159 microRNA (198 detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, survival data). In addition, several tools users analyze mutation profiles, mRNA/microRNA expression, perform gene correlation analyses specific subtypes. This database removes barriers researchers, providing rapid convenient high-quality resources biological applications. CGGA available at http://www.cgga.org.cn.

Language: Английский

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Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes

Cell, Journal Year: 2020, Volume and Issue: 181(7), P. 1626 - 1642.e20

Published: May 28, 2020

Language: Английский

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Applications of focused ultrasound in the brain: from thermoablation to drug delivery

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 17(1), P. 7 - 22

Published: Oct. 26, 2020

Language: Английский

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Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(3), P. 278 - 291

Published: March 1, 2021

Language: Английский

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Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

Cell, Journal Year: 2021, Volume and Issue: 184(9), P. 2454 - 2470.e26

Published: April 1, 2021

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, uncover acquired capability of GSCs to escape clearance by establishing enhanced immunosuppressive microenvironment. Mechanistically, this not elicited via genetic selection subclones, but through epigenetic immunoediting process wherein stable transcriptional and changes are enforced following attack. These launch a myeloid-affiliated program, leads increased recruitment tumor-associated macrophages. Furthermore, identify similar signatures human mesenchymal subtype GSCs. We conclude that may drive program most reshaping

Language: Английский

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Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 4, 2020

Cancer immunotherapy by immune checkpoint blockade has proven its great potential saving the lives of a proportion late stage patients with immunogenic tumor types. However, even in these sensitive types, majority do not sufficiently respond to therapy. Furthermore, other including glioblastoma, remain largely refractory. The glioblastoma microenvironment is recognized as highly immunosuppressive, posing major hurdle for inducing immune-mediated destruction cancer cells. Scattered information available about presence and activity immunosuppressive or immunostimulatory cell types tumors, tumor-associated macrophages, tumor-infiltrating dendritic cells regulatory T These are heterogeneous at level ontogeny, spatial distribution functionality within compartment, providing insight complex cellular molecular interplay that determines refractory state glioblastoma. This knowledge may also yield next generation targets therapeutic intervention.

Language: Английский

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Challenges in glioblastoma research: focus on the tumor microenvironment

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(1), P. 9 - 27

Published: Nov. 16, 2022

Language: Английский

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Trends in glioblastoma: outcomes over time and type of intervention: a systematic evidence based analysis

Journal of Neuro-Oncology, Journal Year: 2020, Volume and Issue: 147(2), P. 297 - 307

Published: March 9, 2020

Language: Английский

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Cannabidiol inhibits human glioma by induction of lethal mitophagy through activating TRPV4

Autophagy, Journal Year: 2021, Volume and Issue: 17(11), P. 3592 - 3606

Published: Feb. 25, 2021

Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against glioma; however, molecular target mechanism of action CBD in glioma are poorly understood. Here we investigated mechanisms underlying antitumor effect preclinical models human glioma. Our results showed that induced autophagic rather than apoptotic cell death cells. We also mitochondrial dysfunction lethal mitophagy arrest, leading death. Mechanistically, calcium flux by through TRPV4 (transient receptor potential cation channel subfamily V member 4) activation played a key role initiation. further confirmed levels correlated both grade patients. Transcriptome analysis other demonstrated ER stress ATF4-DDIT3-TRIB3-AKT-MTOR axis downstream were involved CBD-induced Lastly, temozolomide combination therapy patient-derived neurosphere cultures mouse orthotopic significant synergistic controlling size improving survival. Altogether, these findings for first time caused identified as biomarker Given low toxicity high tolerability CBD, therefore propose should tested clinically glioma, alone temozolomide.Abbreviations: 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; ATF4: activating transcription factor 4; Baf-A1: bafilomycin A1; CANX: calnexin; CASP3: caspase 3; CAT: catalase; CBD: cannabidiol; CQ: chloroquine; DDIT3: DNA damage inducible transcript ER: endoplasmic reticulum; GBM: glioblastoma multiforme; GFP: green fluorescent protein; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic rapamycin PARP1: poly(ADP-ribose) polymerase; PINK1: PTEN kinase 1; PRKN: parkin RBR E3 ubiquitin ligase; SLC8A1: solute carrier family 8 SQSTM1: sequestosome TCGA: cancer genome atlas; TEM: transmission electron microscopy; TMZ: temozolomide; TRIB3: tribbles pseudokinase TRPC: transient C; TRPV4: 4.

Language: Английский

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