Journal of Extracellular Vesicles最新文献

{"title":"Neuronal Apoptotic Bodies Facilitate Japanese Encephalitis Virus Infection and Pathogenicity.","authors":"Chuan Zeng, Xiaowei Nan, Ting Wang, Junyao Xiong, Shuo Zhu, Chengjie Yang, Bibo Zhu, Youhui Si, Shengbo Cao, Jing Ye","doi":"10.1002/jev2.70366","DOIUrl":"10.1002/jev2.70366","url":null,"abstract":"<p><p>Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) infection remains one of the major types of viral encephalitis. The mechanisms underlying JEV infection and pathogenesis have not been fully elucidated, resulting in the absence of specific therapies for JE. Neuronal apoptosis is a well-established outcome of JEV infection; however, its secondary contributions to JE pathogenesis remain largely uncharacterized. Here, we demonstrate that apoptotic bodies (ApoBDs) derived from JEV-infected neurons package infectious JEV particles, facilitating viral transmission between neurons, as well as between neurons and microglia. Further investigations revealed that microglia predominantly internalize the ApoBDs via phagocytosis and dynamin 2-dependent endocytosis. Moreover, lipids, rather than nucleic acids or proteins, are the key pro-inflammatory constituents of ApoBDs. Subsequent studies demonstrated that ApoBDs activate microglia through the TLR2/TLR4-NF‑κB signalling. In vivo experiments showed that JEV-loaded ApoBDs elicit significantly more severe neuroinflammation and pathological lesions compared to ApoBD-free virions. These findings underscore the non-negligible contribution of neuron-derived ApoBDs to JEV pathogenesis, providing valuable insights for the development of novel therapeutic strategies against JE.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":"e70366"},"PeriodicalIF":21.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Extracellular Vesicle and Total Lipid Profiles Provide a Diagnostic Advantage Over CA-125 Across Ovarian Cancer Subtypes.","authors":"Shikha Rani, Dominic Guanzon, Andrew Lai, Katherin Scholz-Romero, Lewis Perrin, Rohan Lourie, Vaibhavi Joshi, Amy E McCart Reed, Kaltin Ferguson, Aase Handberg, Andreas Möller, Carlos Salomon","doi":"10.1002/jev2.70348","DOIUrl":"10.1002/jev2.70348","url":null,"abstract":"<p><p>Ovarian cancer remains the most lethal gynaecological malignancy, largely due to late-stage diagnosis and the limited sensitivity of CA-125 for borderline and low-grade tumours. Dysregulated lipid metabolism may provide complementary diagnostic information. This study aimed to develop lipid-based biomarkers to improve the differential diagnosis of adnexal masses. We profiled total plasma and small extracellular vesicle (sEV) lipids in women with benign, borderline and malignant ovarian tumours, using healthy women as controls. Solid-phase extraction demonstrated superior reproducibility, lipid-class specificity and sEV lipid enrichment compared with liquid-liquid extraction. Combined with CA-125, both plasma and sEV lipid biomarkers outperformed CA-125 alone for distinguishing borderline and low-grade serous ovarian cancer from benign tumours (accuracy up to 0.89 vs. 0.67). In patients with normal CA-125 levels, sEV lipids provided the greatest diagnostic advantage, distinguishing invasive and borderline tumours from benign adnexal masses (AUROC up to 0.82). Generative artificial intelligence was used to simulate biomarker performance in synthetic cohorts for differential diagnosis (n = 10,000) and screening (n = 100,000). For differential diagnosis, sEV lipids combined with CA-125 outperformed plasma lipids for identifying endometrioid and mucinous ovarian cancer from benign adnexal masses. For screening, sEV lipids alone achieved accuracies of 0.91 and 0.94 for benign conditions and high-grade serous ovarian cancer, respectively. Simulations restricted to patients with normal CA-125 levels confirmed that sEV lipids provided the highest discriminative performance for low-grade serous ovarian cancer (AUROC up to 0.74), demonstrating their potential where CA-125 alone fails. To the best of our knowledge, this is the first study to directly compare matched plasma and sEV lipid profiles across ovarian cancer histotypes, demonstrating a diagnostic advantage for sEV lipids-particularly for borderline, low-grade serous and mucinous tumours, supporting their integration alongside CA-125 in future differential diagnosis and screening strategies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":"e70348"},"PeriodicalIF":21.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bovine Colostrum-Derived Extracellular Vesicles Impair Cancer Cell Proliferation Through Transcriptional Dysregulation.","authors":"Claudia Betsabé Huesa-Carballo, Bruno Puga, Susana Bravo, Manuel Rodríguez-Pérez, Yessica Domínguez-Novoa, Julio Iglesias-García, Brígida Hermida, Isolina Raña, María Teresa Antelo, Rafael López-López, Miguel Abal, Jorge Barbazán","doi":"10.1002/jev2.70361","DOIUrl":"10.1002/jev2.70361","url":null,"abstract":"<p><p>Milk-derived extracellular vesicles (EVs) are a promising source of molecules with therapeutic potential. Bovine colostrum is particularly enriched in EVs, which carry cargo of proteins involved in immune regulation, development and cellular signalling. Some studies have explored their role as bioactive anti-cancer agents, however, their mechanistic effects remain underexplored. Here, we show that colostrum-derived EVs (Col-EVs) exert anti-proliferative effects in gastrointestinal cancer models, including cell lines and patient-derived organoids, which is independent of apoptosis induction. Using a multi-modal approach combining proteomics, imaging and functional assays, we demonstrate that Col-EVs induce a reversible growth-arrest state, characterized by widespread transcriptional and RNA-processing dysregulation, chromatin compaction, nuclear reorganization and cytoskeletal remodelling. Proteomic analyses reveal that Col-EV treatment disrupts key components of the transcriptional machinery and cell cycle regulatory pathways, effects that are reversible upon EV withdrawal and can be rescued pharmacologically using an EZH2 inhibitor. Col-EVs enhance the sensitivity of cancer cells as well to DNA-targeting chemotherapies such as 5-fluorouracil, indicating their potential as modulatory adjuvants rather than cytotoxic agents. Overall, our findings reveal that Col-EVs can reversibly suppress cancer cell proliferation by reprogramming transcriptional and nuclear architecture, offering a natural, biocompatible strategy for modulating tumour growth and sensitizing cancer cells to conventional therapies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":"e70361"},"PeriodicalIF":21.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALY688 Protects Against Myocardial Ischemia-Reperfusion Injury via Direct Effects and Rab8a-Dependent Extracellular Vesicles","authors":"Hye Kyoung Sung,&nbsp;Jialing Tang,&nbsp;Yubin Lei,&nbsp;Khang Nguyen,&nbsp;Eddie Tam,&nbsp;Jun Wu,&nbsp;Ren-Ke Li,&nbsp;Vincent Richard,&nbsp;Christoph H. Borchers,&nbsp;Lina Antounians,&nbsp;Dylan Burger,&nbsp;Augusto Zani,&nbsp;Gary Sweeney","doi":"10.1002/jev2.70357","DOIUrl":"https://doi.org/10.1002/jev2.70357","url":null,"abstract":"<p>Despite advances in percutaneous coronary intervention, ischemia-reperfusion (IR) injury remains a major cause of morbidity and mortality. Adiponectin confers broad cardioprotective effects, motivating the development of adiponectin receptor agonists. Here, we investigated the cardioprotective efficacy and mechanisms of ALY688, a synthetic adiponectin receptor agonist peptide, in myocardial IR injury. In a clinically translatable rat IR model, intravenous administration of ALY688 during ischemia together with subcutaneous dosing that continued for 28 days reduced troponin-I levels, cardiomyocyte death, and infarct size, while preserving cardiac function. ALY688 restored autophagic flux, mitigated reactive oxygen species accumulation, and suppressed apoptosis in both IR hearts and hypoxia-reoxygenation (HR)-treated cardiomyocytes. Proteomic profiling revealed that Rab8a, downregulated by IR, was maintained with ALY688 treatment. Notably, ALY688 increased extracellular vesicle (EV) abundance in myocardium and plasma, and EVs from treated animals displayed distinct proteomic signatures enriched in glycolytic and oxidative stress-related proteins. These EVs conferred protection against HR-induced injury in H9c2 and human iPSC-derived cardiomyocytes. CRISPR-mediated Rab8a knockout impaired ALY688-induced EV biogenesis and attenuated the cytoprotective effects of these EVs. Collectively, these findings identify ALY688 as a promising therapeutic that mitigates IR injury via both direct myocardial protection and Rab8a-dependent EV-mediated cardioprotective signalling.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Inhibition of Small Extracellular Vesicle Secretion by ALK5i SD-208 via Lysosomal Rerouting of CD63+ Compartments","authors":"Rahul Sanwlani,&nbsp;Georgina H. Thompson,&nbsp;Kyle Bramich,&nbsp;Ching-Seng Ang,&nbsp;Millie L. Trowbridge,&nbsp;Chris E. Duringer,&nbsp;Vlad Stolojan,&nbsp;Sean M. Davidson,&nbsp;Konstantinos Savvatis,&nbsp;John H. McVey,&nbsp;Suresh Mathivanan,&nbsp;Aled Clayton,&nbsp;Patrizia Camelliti","doi":"10.1002/jev2.70362","DOIUrl":"https://doi.org/10.1002/jev2.70362","url":null,"abstract":"<p>Pharmacological tools to selectively modulate extracellular vesicle (EV) secretion are scarce. Here, we identify the ALK5 (TGF-β receptor I) inhibitor SD-208 as a potent suppressor of small EV (sEV) secretion that acts independently of its canonical anti-fibrotic activity. SD-208 not only reversed myofibroblast activation but also markedly inhibited sEV secretion. Strikingly, this inhibitory effect persisted in non-activated cardiac fibroblasts and non-fibrotic HEK293 cells, demonstrating that SD-208 regulates EV secretion through mechanisms uncoupled from TGF-β/Smad signalling. Mechanistic analyses revealed that SD-208 disrupts vesicle trafficking rather than EV biogenesis. Reduced secretion of CD63⁺ EVs was accompanied by intracellular accumulation of CD63⁺ structures and their selective diversion into LAMP1⁺ lysosomes. Proteomic profiling of SD-208-treated and control HEK293 cells and cardiac fibroblasts revealed dysregulation of vesicle trafficking pathways, enrichment of ubiquitin ligase complexes, and enhanced endosome-to-lysosome transport. Together, these findings demonstrate that SD-208 diverts CD63⁺ multivesicular bodies (MVBs) from a secretory fate toward lysosomal degradation. This work identifies SD-208 as a small-molecule tool to interrogate the secretory-versus-degradative fate of MVBs and uncovers a new regulatory link between lysosomal pathways and EV trafficking. Beyond its established role as an anti-fibrotic agent, SD-208 provides mechanistic and therapeutic opportunities for the control of EV secretion in diseases such as fibrosis, cardiac remodelling, hypertrophic cardiomyopathy, and cancer.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “S100A9 Aggravates Cardiac Fibrosis by TLR4/PGC-1α Mediated Macrophage-Myofibroblast Crosstalk”","authors":"","doi":"10.1002/jev2.70360","DOIUrl":"https://doi.org/10.1002/jev2.70360","url":null,"abstract":"<p>Zhao, Y., Y. Zhang, Q. Yuan, et al. 2026. “S100A9 Aggravates Cardiac Fibrosis by TLR4/PGC-1α Mediated Macrophage-Myofibroblast Crosstalk.” <i>Journal of Extracellular Vesicles</i> 15, no. 7: e70338. https://doi.org/10.1002/jev2.70338</p><p>In the originally published article, statistical significance markers were missing from Figures 1Q and 6G. The correct figures appear below. The online version of the article has been updated.</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-to-Pathogen Transfer of Neutrophil Components via Extracellular Vesicles Shields Candida albicans From Immune Attack in Human Blood","authors":"Jennifer J. Patitz,&nbsp;Natalie E. Nieuwenhuizen,&nbsp;Anastasia Solomatina,&nbsp;Yann Bachelot,&nbsp;Thomas Krüger,&nbsp;Carl-Magnus Svensson,&nbsp;Stephanie Hoeppener,&nbsp;Ann-Kathrin Zimmermann,&nbsp;Matthew G. Blango,&nbsp;Ronny Martin,&nbsp;Olaf Kniemeyer,&nbsp;Theresa Lange,&nbsp;Axel A. Brakhage,&nbsp;Marc Thilo Figge,&nbsp;Oliver Kurzai,&nbsp;Kerstin Hünniger-Ast","doi":"10.1002/jev2.70363","DOIUrl":"https://doi.org/10.1002/jev2.70363","url":null,"abstract":"<p>Neutrophils effectively eliminate <i>Candida albicans</i> from human blood, but a subset of fungal cells escapes clearance and remains extracellular and viable. Here we show that this evasion is independent of known immune-escape traits of <i>C. albicans</i>. Instead, neutrophil-derived extracellular vesicles (EVs) enriched in antimicrobial proteins and neutrophil surface markers (CD66b, CD45, CD63, and complement receptors CR1, CR3 and CR4) promote this state. Isolated EVs bound to <i>C. albicans</i> preferentially in a complement-dependent manner, and this binding was partially inhibited by anti-CD11b, supporting CR3 involvement. Despite their antimicrobial cargo, EVs did not impair fungal growth. Instead, EV coating reduced neutrophil phagocytosis in purified-cell and whole-blood settings. These findings reveal a dual role for neutrophil-derived EVs at the host-pathogen interface: although enriched for innate effector molecules with potential antifungal activity, their deposition on <i>C. albicans</i> does not impair growth but is associated with reduced phagocytosis and maintenance of an extracellular population.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Packaging of miR-22 and miR-29 Orthologues into Extracellular Vesicles of the Porcine Whipworm Trichuris Suis","authors":"Bradley Whitehead,&nbsp;Maibritt Mardahl,&nbsp;Eline P. Hansen,&nbsp;Bastian Fromm,&nbsp;Anne Borup,&nbsp;Anders Toftegaard Boysen,&nbsp;Jasmine C. L. Atay,&nbsp;Rikke Nørregaard,&nbsp;Allan Stensballe,&nbsp;Sidsel D. Andersen,&nbsp;Robin B. Gasser,&nbsp;Marco Brucale,&nbsp;Francesco Valle,&nbsp;Andrea Ridolfi,&nbsp;Eske Nøhr Glud,&nbsp;Merete Fredholm,&nbsp;Andrew R. Williams,&nbsp;Stig M. Thamsborg,&nbsp;Johan Palmfedt,&nbsp;Peter Nejsum","doi":"10.1002/jev2.70351","DOIUrl":"https://doi.org/10.1002/jev2.70351","url":null,"abstract":"<p>Helminths modulate host immunity, and in this respect, the porcine whipworm Trichuris suis has been explored clinically as an immunotherapy for inflammatory diseases. <i>T. suis</i> secretes a complex mixture of excretory/secretory products (ESP), including extracellular vesicles (EVs), nanosized membranous particles with bioactive cargoes of lipids, proteins and nucleic acids that are implicated in intercellular communication within organisms. Here, we characterise the EV protein and miRNA cargo of T. suis to identify potential roles in host–parasite communication. In contrast to EVs from clade III/V helminth species characterised to date, we show that T. suis EVs did not suppress LPS-induced TNF production by human macrophages under the conditions tested, in contrast to non-vesicular ESP fractions which did. By generating the first extracellular miRNA complement for T. suis and quantifying EV-associated versus free miRNAs across larval and adult stages, we identify selective enrichment of two miRNAs in adult EVs with homology to human miR-22-3p and miR-29-3p, canonical anti-fibrotic and tumour-suppressor miRNAs. Functional assays in human colon cancer epithelial cells reveal that these helminth-derived orthologues downregulate conserved oncogenic targets, indicating evolutionary conservation of their regulatory capacity. Our findings uncover a previously unrecognised axis of whipworm biology in which selective EV-mediated export of anti-fibrotic miRNAs has the potential to modulate host tissue remodeling independently of classical immunomodulation, with implications for understanding helminth-driven epithelial homeostasis and cancer risk.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis-Amplified Decoy Nanovesicles Orchestrate Pyroptotic Antigen Explosion and Endogenous Immune Revitalization for Potentiating Tumour Immunotherapy","authors":"Geng Dou,&nbsp;Jiani Liu,&nbsp;Ran Tian,&nbsp;Keying Zhang,&nbsp;Meng Suo,&nbsp;Ding Zhou,&nbsp;Yipeng Zhang,&nbsp;Xuemei Liu,&nbsp;Xinyu Qiu,&nbsp;Jinxin Kuang,&nbsp;Zhaonan Zou,&nbsp;Shuchang Wang,&nbsp;Lu Zhao,&nbsp;Feng Ding,&nbsp;Di Wang,&nbsp;Congcong Guan,&nbsp;Xiaoyu Zhu,&nbsp;Dongyao Wang,&nbsp;Siying Liu,&nbsp;Tianfu Zhang,&nbsp;Yimin Zhao,&nbsp;Shiyu Liu","doi":"10.1002/jev2.70356","DOIUrl":"https://doi.org/10.1002/jev2.70356","url":null,"abstract":"<p>Current advances in tumour immunotherapy remain constrained by inadequate cytotoxic T lymphocyte activation and the immunosuppressive tumour microenvironment. Innovative strategies are urgently required to enhance anti-tumour immune potency for clinical improvements in immunotherapy-resistant malignancies. Herein, we developed pyroptosis-amplified decoy nanovesicles (PADVs) to synergistically dismantle tumour resistance mechanisms and rejuvenate endogenous anti-tumour immunity. PADVs integrate checkpoint-neutralizing capability with precise regulation of the pyroptosis molecular switch in tumour cells, thereby initiating a sequential activation cascade that enables efficient presentation of tumour-specific antigens to the reshaped immune system. Systemically infused PADVs demonstrated dual-targeting priority towards lymph node and deep tumour tissues, reversing immunosuppression through competitive blockade of PD-1/PD-L1 and SIRPα/CD47 axes while providing co-stimulatory signals for immune reactivation. Furthermore, PADVs alleviate the epigenetic suppression of pyroptosis in tumours via cytosolic delivery of decitabine and LPS, enabling gasdermin D (GSDMD) upregulation and cleavage. This coordinated strategy reverses T cell exhaustion and triggers explosive antigen release via GSDMD-mediated membrane perforation, initiating a self-amplifying immune cascade involving dendritic cell activation, effector and memory T cell formation. Consequently, PADVs demonstrate excellent efficacy in suppressing tumour progression, recurrence, and metastasis in melanoma, breast cancer, and colon cancer models. This study pioneers a versatile nanoplatform that not only counteracts tumour immune evasion but also establishes durable anti-tumour immunity, offering a transformative approach to tumour immunotherapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NF1 Leucine Rich Domain-Derived Extracellular Vesicles Remodel the Glioblastoma Immune Microenvironment via an ADAM17-Associated Inflammatory Program","authors":"Yuganthini Vijayanathan,&nbsp;Jacqueline YT Yeo,&nbsp;Janice HY Tan,&nbsp;Fikri Bin Mohamed,&nbsp;Bernett Lee,&nbsp;Tatsuya Kozaki,&nbsp;Nurashikin Abdul Halim,&nbsp;Rachel LY Ho,&nbsp;Hai Tao Tu,&nbsp;Zhi Wei Zhang,&nbsp;Jann N. Sarkaria,&nbsp;Li Zeng,&nbsp;Florent Ginhoux,&nbsp;Ivy AW Ho","doi":"10.1002/jev2.70355","DOIUrl":"https://doi.org/10.1002/jev2.70355","url":null,"abstract":"<p>Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication in cancer. We previously demonstrated that re-expression of the leucine-rich domain (LRD) of neurofibromin (NF1) suppresses glioblastoma (GBM) invasion and limits microglia/macrophage infiltration into the tumor microenvironment (TME). Given the central role of tumor-associated microglia/macrophages (TAMs) in GBM progression, we investigated whether NF1-LRD-containing EVs (NF1-LRD-EVs) could modulate TAM function and remodel the TME. Our results showed that NF1-LRD-EVs attenuated microglia and macrophage recruitment in migration assays, consistent with reduced microglia/macrophage recruitment observed <i>in vivo</i>. In parallel, treatment with NF1-LRD-EVs enhanced phagocytic activity of both microglia and iPSC-derived macrophages, accompanied by induction of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and downregulation of immunosuppressive mediators such as Arginase-1 and IL-10. Mechanistically, NF1-LRD-EVs induced ADAM17-associated inflammatory signaling, accompanied by NF-κB activation. Pharmacological inhibition of ADAM17 reduced TNF-α release and attenuated NF-κB activation, supporting a role for ADAM17-dependent signaling in amplifying this inflammatory response. Together, these findings show that NF1-LRD-EVs reprogram TAMs toward a pro-inflammatory phenotype and modulate the GBM immune microenvironment. These results provide a framework for understanding NF1-LRD-EV-mediated immune regulation and support further investigation of EV-mediated immune modulation of the TME.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}