Journal of Extracellular Vesicles最新文献

{"title":"Extracellular vesicles from seminal plasma interact with T cells in vitro and drive their differentiation into regulatory T-cells","authors":"Xiaogang Zhang,&nbsp;Patrick F. Greve,&nbsp;Thi Tran Ngoc Minh,&nbsp;Richard Wubbolts,&nbsp;Ayşe Y. Demir,&nbsp;Esther A. Zaal,&nbsp;Celia R. Berkers,&nbsp;Marianne Boes,&nbsp;Willem Stoorvogel","doi":"10.1002/jev2.12457","DOIUrl":"10.1002/jev2.12457","url":null,"abstract":"<p>Seminal plasma induces immune tolerance towards paternal allogenic antigens within the female reproductive tract and during foetal development. Recent evidence suggests a role for extracellular vesicles in seminal plasma (spEVs). We isolated spEVs from seminal plasma that was donated by vasectomized men, thereby excluding any contributions from the testis or epididymis. Previous analysis demonstrated that such isolated spEVs originate mainly from the prostate. Here we observed that when isolated fluorescently labelled spEVs were mixed with peripheral blood mononuclear cells, they were endocytosed predominantly by monocytes, and to a lesser extent also by T-cells. In a mixed lymphocyte reaction, T-cell proliferation was inhibited by spEVs. A direct effect of spEVs on T-cells was demonstrated when isolated T cells were activated by anti-CD3/CD28 coated beads. Again, spEVs interfered with T cell proliferation, as well as with the expression of CD25 and the release of IFN-γ, TNF, and IL-2. Moreover, spEVs stimulated the expression of Foxp3 and IL-10 by CD4+CD25+CD127- T cells, indicating differentiation into regulatory T-cells (Tregs). Prior treatment of spEVs with proteinase K revoked their effects on T-cells, indicating a requirement for surface-exposed spEV proteins. The adenosine A2A receptor-specific antagonist CPI-444 also reduced effects of spEVs on T-cells, consistent with the notion that the development of Tregs and their immune suppressive functions are under the influence of adenosine-A2A receptor signalling. We found that adenosine is highly enriched in spEVs and propose that spEVs are targeted to and endocytosed by T-cells, after which they may release their adenosine content into the lumen of endosomes, thus allowing endosome-localized A2A receptor signalling in spEVs targeted T-cells. Collectively, these data support the idea that spEVs can prime T cells directly for differentiation into Tregs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616604","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":"ISEV2024 Abstract Book","authors":"","doi":"10.1002/jev2.12444","DOIUrl":"10.1002/jev2.12444","url":null,"abstract":"&lt;p&gt;The International Society for Extracellular Vesicles is the leading professional society for researchers and scientists involved in the study of microvesicles and exosomes. With nearly 1,000 members, ISEV continues to be the leader in advancing the study of extracellular vesicles. Founded in 2012 in Sweden, ISEV has since moved its Headquarters to the United States. Through its programs and services, ISEV provides essential training and research opportunities for those involved in exosome and microvesicle research.&lt;/p&gt;&lt;p&gt;Advancing extracellular vesicle research globally.&lt;/p&gt;&lt;p&gt;Our vision is to be the leading advocate and guide of extracellular vesicle research and to advance the understanding of extracellular vesicle biology.&lt;/p&gt;&lt;p&gt;The International Society for Extracellular Vesicles is the is the premier international conference of extracellular vesicle research, covering the latest in exosomes, microvesicles and more. With an anticipated 1,000+ attendees, ISEV2024 will feature presentations from the top researchers in the field, as well as providing opportunities for talks from students and early career researchers.&lt;/p&gt;&lt;p&gt;IOC Chairs: Cherie Blenkiron (New Zealand), David Greening (Australia)&lt;/p&gt;&lt;p&gt;IOC Members: Randy Carney (USA), Leslie Cheng (Australia), Eisuke Dohi (Japan), Qing-Ling Fu (China), Charles Lai (Taiwan), Metka Lenassi (Slovenia), Andreas Moeller (China), Jisook Moon (South Korea), Natalie Turner (Australia)&lt;/p&gt;&lt;p&gt;Jan Lötvall (Sweden)&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O02&lt;/b&gt; Cellular interaction and uptake of human endogenous retrovirus (HERV) envelope-displaying EVs&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Zach Troyer&lt;/span&gt;&lt;/b&gt;, Sarah Marquez, PhD Olesia Gololobova, PhD Kenneth Witwer&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O03&lt;/b&gt; Functionalized engineered extracellular vesicles for targeted delivery to intervertebral disc cells&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Ms Mia Kordowski&lt;/span&gt;&lt;/b&gt;, Dr Ana Salazar-Puerta, Ms María Rincon-Benavides, Mr Justin Richards, Dr Nina Tang, Dr Safdar Khan, Dr Elizabeth Yu, Dr Judith Hoyland, Dr Devina Purmessur, Dr Natalia Higuita-Castro&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O04&lt;/b&gt; Phospholipid scrambling: a novel regulator of extracellular vesicle cargo packaging and function&lt;/p&gt;&lt;p&gt;Ms Akbar Marzan, Ms Monika Petrovska, Professor Suresh Mathivanan, &lt;b&gt;&lt;span&gt;Sarah Stewart&lt;/span&gt;&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;0T04.O05&lt;/b&gt; Quantitative features of extracellular vesicle-mediated crosstalk in multi-cellular 3D tumor models&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Maria Harmati&lt;/span&gt;&lt;/b&gt;, Akos Diosdi, Ferenc Kovács, Ede Migh, Gabriella Dobra, Timea Boroczky, Matyas Bukva, Edina Gyukity-Sebestyen, Peter Horvath, Krisztina Buzas&lt;/p&gt;&lt;p&gt;&lt;b&gt;FA01&lt;/b&gt; Extracellular vesicles in human body fluids compete with virus particles for binding of phosphatidylserine receptors to prevent infection and transmission&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;span&gt;Dr. Ruediger Gross&lt;/span&gt;&lt;/b&gt;, Hanna Reßin, Pascal von Maltitz, Dan Albers, Laura Schneider, Hanna Bley, Markus Hoffmann, Mirco Cortese, Dhanu Gupta, Miriam Deniz, Jae-Yeon Choi, Jenny Jansen, Christian Preußer, Kai Seehafer, Stefan Pö","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 S1","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600198","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":"Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis","authors":"Heetanshi Jain,&nbsp;Ashish Kumar,&nbsp;Sameh Almousa,&nbsp;Shalini Mishra,&nbsp;Kendall L. Langsten,&nbsp;Susy Kim,&nbsp;Mitu Sharma,&nbsp;Yixin Su,&nbsp;Sangeeta Singh,&nbsp;Bethany A. Kerr,&nbsp;Gagan Deep","doi":"10.1002/jev2.12474","DOIUrl":"10.1002/jev2.12474","url":null,"abstract":"<p>Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra-intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter-kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEV^LPS) from complex biological samples, including faeces, plasma and the liver from lean and diet-induced obese (DIO) mice. bEV^LPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super-resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage-specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation-related cytokines and their receptors (<i>n</i> = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEV^LPS showed a higher abundance of <i>Proteobacteria</i> by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEV^LPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (<i>Il1rn</i>, <i>Ccr1</i>, <i>Cxcl10</i>, <i>Il2rg</i> and <i>Ccr2</i>). Furthermore, a portion of bEV^LPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well-established biological effects induced by gut bacteria on distant organs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603713","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":"Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles","authors":"Liqiao Hu,&nbsp;Xinyue Zheng,&nbsp;Maoge Zhou,&nbsp;Jifeng Wang,&nbsp;Lingjun Tong,&nbsp;Ming Dong,&nbsp;Tao Xu,&nbsp;Zonghong Li","doi":"10.1002/jev2.12470","DOIUrl":"10.1002/jev2.12470","url":null,"abstract":"<p>Extracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV-associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field-flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high-purity and intact EVs with very low lipoprotein contamination from human plasma and serum. Further proteomic analysis revealed more than 1000 EV-associated proteins, a large proportion of which has not been previously reported. Specifically, we found that cell-line-derived EV markers are incompatible with the identification of plasma-EVs and proposed that the proteins MYCT1, TSPAN14, MPIG6B and MYADM, as well as the traditional EV markers CD63 and CD147, are plasma-EV markers. Benefiting from the high-purity of EVs, we conducted comprehensive miRNA profiling of plasma EVs and nanosized particles (NPs), as well as compared plasma- and serum-derived EVs, which provides a valuable resource for the EV research community. Overall, our findings provide a comprehensive assessment of human blood EVs as a basis for clinical biopsy applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603714","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":"Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation","authors":"Joël E. J. Beaumont,&nbsp;Lydie M. O. Barbeau,&nbsp;Jinzhe Ju,&nbsp;Kim G. Savelkouls,&nbsp;Freek G. Bouwman,&nbsp;Marijke I. Zonneveld,&nbsp;Annelies Bronckaers,&nbsp;Kim R. Kampen,&nbsp;Tom G. H. Keulers,&nbsp;Kasper M. A. Rouschop","doi":"10.1002/jev2.12449","DOIUrl":"10.1002/jev2.12449","url":null,"abstract":"<p>Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603712","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":"Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles","authors":"Zainuddin Quadri,&nbsp;Ahmed Elsherbini,&nbsp;Simone M. Crivelli,&nbsp;Salim S. El-Amouri,&nbsp;Priyanka Tripathi,&nbsp;Zhihui Zhu,&nbsp;Xiaojia Ren,&nbsp;Liping Zhang,&nbsp;Stefka D. Spassieva,&nbsp;Mariana Nikolova-Karakashian,&nbsp;Erhard Bieberich","doi":"10.1002/jev2.12477","DOIUrl":"10.1002/jev2.12477","url":null,"abstract":"<p>Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H₂O₂ in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopodia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of nSMase2 and ASM prevented oxidative stress-induced sEV shedding but only nSMase2 inhibition prevented filopodia formation. nSMase2 was S-palmitoylated and interacted with ASM in filopodia to generate ceramide for sEV shedding. sEVs contained nSMase2 and ASM and decreased the level of these two enzymes in oxidatively stressed Hela cells. A novel metabolic labeling technique for EVs showed that oxidative stress induced secretion of fluorescent sEVs labeled with NBD-ceramide. NBD-ceramide-labeled sEVs transported ceramide to mitochondria, ultimately inducing cell death in a proportion of neuronal (N2a) cells. In conclusion, using Hela cells we provide evidence that oxidative stress induces interaction of nSMase2 and ASM at filopodia, which leads to shedding of ceramide-rich sEVs that target mitochondria and propagate cell death.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579891","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":"Connecting through ISEV's developing social media landscape","authors":"Tom. A. P. Driedonks,&nbsp;Deborah C. I. Goberdhan,&nbsp;Sujata Mohanty,&nbsp;Sarah Williams,&nbsp;Rienk Nieuwland,&nbsp;Kenneth W. Witwer,&nbsp;Ana Claudia Torrecilhas","doi":"10.1002/jev2.12475","DOIUrl":"10.1002/jev2.12475","url":null,"abstract":"<p>Social media are indispensable for organizations which communicate to a wide target audience. ISEV has been active on social media since it was founded in 2011. As we approach ISEV's 10-year anniversary on social media platform X, formerly known as Twitter, the members of ISEV's Communications Committee (2022-2024) evaluated how ISEV has used social media to convey the voice of the Society and its members, as well as looking to the future and how things may change and develop in the years to come.</p><p>We hope this editorial inspires you to “connect,” “like,” and “tweet” with us and other EV enthusiasts on social media.</p><p><b>Tom Driedonks</b>: Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); project administration (lead); resources (equal); software (equal); supervision (lead); validation (equal); visualization (equal); writing—original draft (lead); writing—review and editing (lead). <b>Deborah Goberdhan</b>: Conceptualization (equal); formal analysis (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Sujata Mohanty</b>: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Sarah Williams</b>: Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Rienk Nieuwland</b>: Data curation (equal); formal analysis (equal); investigation (equal); project administration (equal); resources (equal); software (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Kenneth Witwer</b>: Data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); resources (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). <b>Ana Torrecilhas</b>: Conceptualization (lead); data curation (equal); formal analysis (equal); funding acquisition (lead); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (lead); validation (equal); visualization (equal); writing—original draft (lead); writing—review and editing (lead).</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558883","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":"Extracellular vesicle isolation and counting system (EVics) based on simultaneous tandem tangential flow filtration and large field-of-view light scattering","authors":"Ju-Hyun Bae,&nbsp;Chan-Hyeong Lee,&nbsp;Dokyung Jung,&nbsp;Kyungmoo Yea,&nbsp;Byoung-Joon Song,&nbsp;Hakho Lee,&nbsp;Moon-Chang Baek","doi":"10.1002/jev2.12479","DOIUrl":"10.1002/jev2.12479","url":null,"abstract":"<p>Although the isolation and counting of small extracellular vesicles (sEVs) are essential steps in sEV research, an integrated method with scalability and efficiency has not been developed. Here, we present a scalable and ready-to-use extracellular vesicle (EV) isolation and counting system (EVics) that simultaneously allows isolation and counting in one system. This novel system consists of (i) EVi, a simultaneous tandem tangential flow filtration (TFF)-based EV isolation component by applying two different pore-size TFF filters, and (ii) EVc, an EV counting component using light scattering that captures a large field-of-view (FOV). EVi efficiently isolated 50–200 nm-size sEVs from 15 µL to 2 L samples, outperforming the current state-of-the-art devices in purity and speed. EVc with a large FOV efficiently counted isolated sEVs. EVics enabled early observations of sEV secretion in various cell lines and reduced the cost of evaluating the inhibitory effect of sEV inhibitors by 20-fold. Using EVics, sEVs concentrations and sEV PD-L1 were monitored in a 23-day cancer mouse model, and 160 clinical samples were prepared and successfully applied to diagnosis. These results demonstrate that EVics could become an innovative system for novel findings in basic and applied studies in sEV research.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558884","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":"Extracellular vesicle isolation methods identify distinct HIV-1 particles released from chronically infected T-cells","authors":"Sebastian M. Molnar,&nbsp;Yuriy Kim,&nbsp;Lindsay Wieczorek,&nbsp;Anastasia Williams,&nbsp;Kajal Ashok Patil,&nbsp;Pooja Khatkar,&nbsp;Mark F. Santos,&nbsp;Gifty Mensah,&nbsp;Aurelio Lorico,&nbsp;Victoria R. Polonis,&nbsp;Fatah Kashanchi","doi":"10.1002/jev2.12476","DOIUrl":"10.1002/jev2.12476","url":null,"abstract":"<p>The current study analyzed the intersecting biophysical, biochemical, and functional properties of extracellular particles (EPs) with the human immunodeficiency virus type-1 (HIV-1) beyond the currently accepted size range for HIV-1. We isolated five fractions (Frac-A through Frac-E) from HIV-infected cells by sequential differential ultracentrifugation (DUC). All fractions showed a heterogeneous size distribution with median particle sizes greater than 100 nm for Frac-A through Frac-D but not for Frac-E, which contained small EPs with an average size well below 50 nm. Synchronized and released cultures contained large infectious EPs in Frac-A, with markers of amphisomes and viral components. Additionally, Frac-E uniquely contained EPs positive for CD63, HSP70, and HIV-1 proteins. Despite its small average size, Frac-E contained membrane-protected viral integrase, detectable only after SDS treatment, indicating that it is enclosed in vesicles. Single particle analysis with dSTORM further supported these findings as CD63, HIV-1 integrase, and the viral surface envelope (Env) glycoprotein (gp) colocalized on the same Frac-E particles. Surprisingly, Frac-E EPs were infectious, and infectivity was significantly reduced by immunodepleting Frac-E with anti-CD63, indicating the presence of this protein on the surface of infectious small EPs in Frac-E. To our knowledge, this is the first time that extracellular vesicle (EV) isolation methods have identified infectious small HIV-1 particles (_smHIV-1) that are under 50 nm. Collectively, our data indicate that the crossroads between EPs and HIV-1 potentially extend beyond the currently accepted biophysical properties of HIV-1, which may have further implications for viral pathogenesis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558885","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":"The immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer","authors":"Dominique S. Rubenich,&nbsp;Jordana L. Domagalski,&nbsp;Gabriela F. S. Gentil,&nbsp;Jonas Eichberger,&nbsp;Mathias Fiedler,&nbsp;Florian Weber,&nbsp;Marianne Federlin,&nbsp;Hendrik Poeck,&nbsp;Torsten E. Reichert,&nbsp;Tobias Ettl,&nbsp;Richard J. Bauer,&nbsp;Elizandra Braganhol,&nbsp;Daniela Schulz","doi":"10.1002/jev2.12480","DOIUrl":"10.1002/jev2.12480","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) is a global cancer burden with a 5-year overall survival rate of around 50%, stagnant for decades. A tumour-induced immunosuppressive microenvironment contributes to HNSCC progression, with the adenosine (ADO) pathway and an upregulated expression of inhibitory immune checkpoint regulators playing a key role in this context. The correlation between high neutrophil-to-lymphocyte ratio (NLR) with advanced tumour staging suggests involvement of neutrophils (NØ) in cancer progression. Interestingly, we associated a high NLR with an increased intracellular PD-L1 localization in primary HNSCC samples, potentially mediating more aggressive tumour characteristics and therefore synergistically favouring tumour progression. Still, further research is needed to harness this knowledge for effective treatments and overcome resistance. Since it is hypothesized that the tumour microenvironment (TME) may be influenced by small extracellular vesicles (sEVs) secreted by tumours (TEX), this study aims to investigate the impact of HNSCC-derived TEX on NØ and blockade of ADO receptors as a potential strategy to reverse the pro-tumour phenotype of NØ. UMSCC47-TEX exhibited CD73 enzymatic activity involved in ADO signalling, as well as the immune checkpoint inhibitor PD-L1. Data revealed that TEX induce chemotaxis of NØ and the sustained interaction promotes a shift into a pro-tumour phenotype, dependent on ADO receptors (P1R), increasing CD170^high subpopulation, CD73 and PD-L1 expression, followed by an immunosuppressive secretome. Blocking A3R reduced CD73 and PD-L1 expression. Co-culture experiments with HNSCC cells demonstrated that TEX-modulated NØ increase the CD73/PD-L1 axis, through Cyclin D-CDK4/6 signalling. To support these findings, the CAM model with primary tumour was treated with NØ supernatant. Moreover, these NØ promoted an increase in migration, invasion, and reduced cell death. Targeting P1R on NØ, particularly A3R, exhibited potential therapeutic strategy to counteract immunosuppression in HNSCC. Understanding the TEX-mediated crosstalk between tumours and NØ offers insights into immunomodulation for improving cancer therapies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558910","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}