Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.
Astrid De Boeck,Bo Young Ahn,Charlotte D'Mello,Xueqing Lun,Shyam V Menon,Mana Alshehri,Mana Alshehri,Frank Szulzewsky,Yaoqing Shen,Lubaba Khan,Ngoc Ha Dang,Elliott Michael Reichardt,Kimberly-Ann R. Goring,Jennifer King,Cameron J. Grisdale,Natalie Grinshtein,Dolores Hambardzumyan,Karlyne M. Reilly,Michael D. Blough,J. Gregory Cairncross,V. Wee Yong,Marco A. Marra,Steven J.M. Jones,David L. Kaplan,Kathy D. McCoy,Eric C. Holland,Pinaki Bose,Jennifer A. Chan,Stephen M. Robbins,Donna L. Senger +29 more
TLDR
It is found that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia, which supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.Abstract:
Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.read more
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Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy.
Jun Wang,Wei Tang,Meng Yang,Ying Yin,Hui Li,Fangfang Hu,Lin Tang,Xiaoyue Ma,Yu Zhang,Yazhou Wang +9 more
TL;DR: In this article, a bioinspired neutrophil-exosomes (NEs-Exos) system for delivering loaded doxorubicin (DOX) drug for glioma treatment is proposed and systematically investigated.
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Macrophages and microglia: the cerberus of glioblastoma.
TL;DR: In this paper, the authors review the origin, heterogeneity, and functional roles of TAMs and discuss the prospects of therapeutically targeting TAMs alone or in combination with standard or newly emerging GBM targeting therapies.
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Myeloid Cells in Glioblastoma Microenvironment.
TL;DR: In this article, the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, mi-loid-derived suppressor cells, dendritic cells, and neutrophils are reviewed.
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Glial and myeloid heterogeneity in the brain tumour microenvironment.
Brian M Andersen,Brian M Andersen,Camilo Faust Akl,Michael A. Wheeler,Michael A. Wheeler,E. Antonio Chiocca,David A. Reardon,Francisco J. Quintana,Francisco J. Quintana +8 more
TL;DR: In this article, the authors discuss the immune modulatory functions of microglia, monocyte-derived macrophages and astrocytes in brain metastases and glioma.
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Silk Microneedle Patch Capable of On-Demand Multidrug Delivery to the Brain for Glioblastoma Treatment.
Zijing Wang,Zijing Wang,Zhipeng Yang,Jianjuan Jiang,Zhifeng Shi,Ying Mao,Nan Qin,Tiger H. Tao +7 more
TL;DR: In this article, the design, fabrication and application of a heterogenous silk fibroin microneedle (SMN) patch is reported for circumventing the blood-brain barrier and releasing multiple drugs directly to the tumor site for drug combination treatment.
References
More filters
Journal ArticleDOI
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp,Warren P. Mason,Martin J. van den Bent,Michael Weller,Barbara Fisher,Martin J.B. Taphoorn,Karl Belanger,Alba A. Brandes,Christine Marosi,Ulrich Bogdahn,Jürgen Curschmann,Robert C. Janzer,Samuel K. Ludwin,Thierry Gorlia,Anouk Allgeier,Denis Lacombe,J. Gregory Cairncross,Elizabeth Eisenhauer,René O. Mirimanoff +18 more
TL;DR: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Journal ArticleDOI
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
TL;DR: An R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters and can be easily extended to other species and ontologies is presented.
Journal ArticleDOI
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.
Jiirgen Cox,Matthias Mann +1 more
TL;DR: MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data, detects peaks, isotope clusters and stable amino acid isotope–labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space and achieves mass accuracy in the p.p.b. range.
Journal ArticleDOI
Comprehensive Integration of Single-Cell Data.
Tim Stuart,Andrew Butler,Paul J. Hoffman,Christoph Hafemeister,Efthymia Papalexi,William M. Mauck,Yuhan Hao,Marlon Stoeckius,Peter Smibert,Rahul Satija +9 more
TL;DR: A strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities.
Journal ArticleDOI
Integrating single-cell transcriptomic data across different conditions, technologies, and species.
TL;DR: An analytical strategy for integrating scRNA-seq data sets based on common sources of variation is introduced, enabling the identification of shared populations across data sets and downstream comparative analysis.
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