European cytokine network最新文献

{"title":"Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.","authors":"Yuyue Luo, Yikan Zheng, Jie Qin, Jinwei Liu, Yuhan Ma, Jingda Li, Jun Li, Wenlong Sun, Qian Zhang, Mengyao Li","doi":"10.32604/ecn.2026.082885","DOIUrl":"https://doi.org/10.32604/ecn.2026.082885","url":null,"abstract":"<p><p>Cytokines, as key signaling molecules, are involved in the regulation of physiological and pathological processes such as inflammation, immunity, and cell growth. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, enable precise control of gene expression without changing the DNA sequence. Recent studies have revealed that cytokines interact with epigenetic regulation to form a dynamic and complex \"cytokine-epigenetic axis\". Through metabolic reprogramming and regulation of epigenetic enzyme activity, this axis affects gene expression patterns at both transcriptional and post-transcriptional levels, thereby contributing to the initiation and progression of various diseases, including autoimmune diseases, neurodegenerative diseases, neuropsychiatric disorders, metabolic diseases, and cancer. Targeting this regulatory axis by combining interventions on upstream cytokine signaling and downstream epigenetic enzymes represents a new precision therapeutic strategy for overcoming resistance to monotherapy and achieving disease-modifying treatment. This review describes how cytokines regulate epigenetic modification substrates through metabolic reprogramming and directly regulate epigenetic enzyme activity via JAK-STAT, NF-κB, and TGF-β/Smad pathways; how this axis drives disease chronicity and therapy resistance across autoimmune, neurodegenerative, metabolic, and neoplastic diseases by establishing long-lasting functional reprogramming; and emerging strategies targeting this axis through combined interventions, precision medicine, and disease memory reprogramming.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"97-119"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenosialylation as immunological chimerism: a host-centered unifying model for viral and post-vaccination immune complications.","authors":"Fiorella Carnevali, Maria Chiara Muollo, Lucia Biagini, Giacomo Rossi","doi":"10.32604/ecn.2026.082188","DOIUrl":"https://doi.org/10.32604/ecn.2026.082188","url":null,"abstract":"<p><p>Severe immune-mediated complications following viral infections and vaccinations, including COVID-19 and anti-SARS-CoV-2 immunization, display remarkable clinical overlap despite occurring in distinct biological contexts. In a previous hypothesis-driven work, we proposed that metabolic incorporation of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into human glycoconjugates-defined as xenosialylation-may contribute to post-infectious and post-vaccination immune dysregulation. We further suggest that this phenomenon may represent a form of \"immunological chimerism\", in which host glycoconjugates incorporate non-self molecular structures that predispose the immune system to varying degrees of immune imbalance. In its most severe manifestation, this process may culminate in a profound state of immune dysregulation characterized by loss of immune tolerance, aberrant antibody responses, cytokine storm, and thrombo-inflammatory pathology, which we define as \"immunological marasmus\". In the present paper, we extend this conceptual framework by integrating glycobiology, Fc immunoglobulin glycosylation, endothelial biology, and sex-dependent immune regulation into a unified, testable immunopathogenic model. We hypothesize that interindividual differences in the extent, tissue distribution, and persistence of xenosialylation may influence susceptibility to exaggerated innate and adaptive immune responses following antigenic challenge. In this context, immune activation may unmask pre-existing xeno-sialylated self-structures embedded within host glycans, promoting varying degrees of glycan dysregulation, autoantibody production, immunothrombosis and chronic inflammatory sequelae. We further propose circulating anti-Neu5Gc antibodies as functional biomarkers for risk stratification and outline preventive strategies based on dietary modulation of xenosialic acid exposure. Taken together, this expanded model provides a potential mechanistic framework for understanding the shared immunological features of post-viral syndromes and vaccine-related adverse immune reactions, while offering a basis for experimental validation and future approaches to personalized risk mitigation.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"55-77"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging viral infections: role of flavivirus NS1-mediated rewiring of PRR signaling.","authors":"Matteo Ferraresi, Giulia Pezzi, Silvia Beltrami, Giorgia Cianci, Gloria Maini, Alessia Liboni, Marcello Baroni, Daria Bortolotti, Giovanna Schiuma, Sabrina Rizzo, Giovanni Strazzabosco","doi":"10.32604/ecn.2026.083049","DOIUrl":"https://doi.org/10.32604/ecn.2026.083049","url":null,"abstract":"<p><p>Flaviviruses, including Dengue, West Nile, Zika, and Japanese encephalitis viruses, are arthropod-borne RNA viruses that pose an increasing global health threat. This review summarizes the role of nonstructural protein 1 (NS1), a multifunctional glycoprotein found in intracellular and secreted forms, as a key regulator of innate immunity. NS1 modulates several pattern recognition receptor pathways, including TLRs, RLRs, SR-B1-related mechanisms, and inflammasome platforms, thereby altering cytokine and interferon responses. Its effects are virus- and context-dependent. WNV NS1 inhibits TLR3/TRIF signaling, reducing IRF3 activation, type I interferon production, and interferon-stimulated gene expression. In contrast, DENV NS1 is linked to inflammatory signaling, particularly through TLR4. At the cytosolic level, NS1 from DENV, WNV, and ZIKV disrupts RIG-I/MDA5-MAVS signaling and weakens IFN-β induction. NS1 also affects inflammasome pathways: DENV promotes IL-1β release through a CD14-dependent mechanism, ZIKV suppresses cGAS-mediated antiviral signaling, and JEV promotes NLRP3 inflammasome assembly. Overall, NS1 selectively dampens interferon-mediated antiviral defenses while sustaining or enhancing inflammation, contributing to endothelial dysfunction, neuroinflammation, and severe disease.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"41-53"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGFC as a prognostic cytokine biomarker linking lymph node metastasis to immune suppression in breast cancer.","authors":"Hsing-Ju Wu, Yu-Chieh Tsai, Hung-Yu Lin","doi":"10.32604/ecn.2026.079012","DOIUrl":"https://doi.org/10.32604/ecn.2026.079012","url":null,"abstract":"<p><strong>Backgrounds: </strong>Lymph node metastasis is a critical determinant of breast cancer prognosis, yet the specific microenvironmental cytokines driving this process remain elusive. This study aims to identify key prognostic cytokines linking nodal metastasis to tumor microenvironment (TME) remodeling and to evaluate their clinical utility.</p><p><strong>Methods: </strong>A predefined panel of 176 microenvironmental genes was evaluated using differential expression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm on the TCGA-BRCA cohort to identify optimal predictors of nodal metastasis. Prognostic value was assessed via Kaplan-Meier, subgroup, and multivariate Cox regression analyses, and validated across five independent GEO datasets. Immune infiltration and therapeutic potential were evaluated using Gene Set Enrichment Analysis (GSEA), CIBERSORT deconvolution, pharmacogenomic screening, and molecular docking simulations.</p><p><strong>Results: </strong>Vascular Endothelial Growth Factor C (VEGFC) emerged as the top biomarker significantly upregulated in node-positive tumors. Multivariate analysis confirmed that VEGFC acts as a robust, independent predictor of poor relapse-free survival (RFS). Notably, subgroup analyses revealed this prognostic penalty is exceptionally pronounced in hormone receptor-positive Luminal A and B subtypes. Mechanistically, elevated VEGFC is strongly associated with an immunosuppressive \"cold\" TME, characterized by reduced cytotoxic CD8+ T-cell infiltration and enriched M2-macrophage polarization across multiple algorithms. Furthermore, pharmacogenomic analyses and docking simulations indicated potential sensitivity to PI3K/AKT inhibitors in VEGFC-high tumors.</p><p><strong>Conclusions: </strong>VEGFC is a robust, independent precision biomarker specifically indicating poor prognosis in Luminal breast cancers. It is significantly associated with an immune-excluded TME, suggesting that targeting the VEGFC axis may offer a novel strategy to reverse immune evasion.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"121-135"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine signalling in vaginal epithelial cells: mechanistic insights into epithelial immunity and inflammatory milieu in vulvovaginal candidiasis.","authors":"Kavee Shree Sukumaran, Nelli Giribabu, Naguib Salleh","doi":"10.32604/ecn.2026.078477","DOIUrl":"https://doi.org/10.32604/ecn.2026.078477","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC) is one of the most prevalent mucosal infections worldwide, experienced by women throughout their reproductive years. Candida albicans is involved in 85-95% of all VVC cases and given the stronger correlation between the severity of epithelial cytokine responses, rather than fungal burden, with VVC symptoms, this disease is fundamentally immunopathological. VVC is believed to be initiated by a cascade of events that leads to vaginal epithelial cell (VEC) damage. These cells act as immune sentinels and can detect fungal morphotypes as well as virulence factors through diverse pattern recognition receptors, such as TLRs, C-type lectin receptors, and nucleotide-binding oligomerization domain-like receptors. Recognition of C. albicans can trigger complex intracellular signalling cascades in VECs that involve NF-κB, MAPK, and activator protein-1, which culminate in robust production of proinflammatory cytokines, chemokines, and alarmins. The hypha-specific peptide toxin, candidalysin can also initiate VEC membrane damage, which leads to nucleotide-binding oligomerization domain, leucine-rich repeat family and pyrin domain-containing protein 3 inflammasome assembly in the VECs. The resulting inflammatory events lead to robust recruitment of neutrophils, which, although they fail to effectively clear the fungus, add to even more tissue damage, contributing to the severity of VVC symptoms. This review synthesises the molecular- and cellular-based evidence to clarify the role of VEC-related immune activation in the development of VVC and to provide a new understanding that VVC signs and symptoms are predominantly immune-related.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"79-95"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procaine hydrochloride improves DSS-induced colitis via inhibition of IL-6/STAT3 and FOXP3 methylation.","authors":"An Xiong, Yi Tian, Xin Liang, Shaoqun Liu, Chencheng Shi, Yiou Cao, Chang Su","doi":"10.32604/ecn.2026.084018","DOIUrl":"https://doi.org/10.32604/ecn.2026.084018","url":null,"abstract":"<p><strong>Backgrounds: </strong>Disruption of immune barrier function is considered a hallmark feature of inflammatory bowel disease. In the present study, the potential effects of the methyltransferase inhibitor procaine hydrochloride on intestinal barrier integrity, as well as T cell differentiation in the context of inflammatory bowel disease were explored.</p><p><strong>Methods: </strong>Using an experimental model of dextran sulfate sodium-induced ulcerative colitis, mice received daily treatment with either sulfasalazine (100 mg/kg) or procaine hydrochloride (45 mg/kg), or saline (10 μL/g) as a negative control, for 7 consecutive days. Subsequent analysis included disease activity index score, histopathology, expression levels of intestinal epithelial tight junctions and apoptotic protein, production of inflammatory cytokines, frequencies of lymphocyte populations in the spleen by flow cytometry and methylation levels of Forkhead box protein 3 (FOXP3).</p><p><strong>Results: </strong>Procaine alleviated dextran sulfate sodium-induced colitis, with a reduced disease activity index (p < 0.05) and histopathological score (p < 0.001). Procaine treatment resulted in a 1.96-fold increase in splenic FOXP3+ CD25+ Tregs (p < 0.001). Administration of procaine significantly enhanced tight junction expression (p < 0.01), decreased the expression of BAX and cleaved caspase-3 protein expression, while increasing that of the anti-apoptotic protein BCL-2. Procaine also significantly suppressed IL-6/signal transducer and activator of transcription factor 3 (STAT3) signaling pathway. In addition, procaine amplified FOXP3+ Tregs by inhibiting FOXP3 methylation.</p><p><strong>Conclusions: </strong>The protective potential of procaine hydrochloride against intestinal barrier injury in colitis may be attributed to increased abundance of Tregs and the augmentation of their anti-inflammatory properties. The potential mechanisms may involve modulation of IL-6/STAT3 signaling pathway and inhibition of FOXP3 methylation.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 2","pages":"137-149"},"PeriodicalIF":1.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-expression of CCR7 and H3K9me3 identifies aggressive B-cell lymphoma with bone marrow infiltration and poor prognosis.","authors":"Jiawen Chen, Zelin Liu, Keke Huang, Jinlan Li, Yajie Zhang, Dandan Chen, Yanjie Ruan, Ying Pan, Furun An, Yang Wan, Jiyu Wang, Qianshan Tao","doi":"10.32604/ecn.2026.077875","DOIUrl":"10.32604/ecn.2026.077875","url":null,"abstract":"<p><strong>Objectives: </strong>B-cell lymphoma exhibits significant clinical heterogeneity, necessitating improved biomarkers for risk stratification. C-C chemokine receptor 7 (CCR7) and trimethylation of histone H3 lysine 9 (H3K9me3) are implicated in cellular senescence and tumor invasion. While the clinical significance of their co-expression in lymphomagenesis remains unclear. This study aims to define the expression profiles of CCR7 and H3K9me3 in B-cell lymphoma, explore their correlation with aggressive clinical indicators, and evaluate their combined prognostic value.</p><p><strong>Methods: </strong>The expression of CCR7 and H3K9me3 in tumor tissues from B-cell lymphoma patients was analyzed by immunohistochemical (IHC) double-staining. The mechanistic association between the two was verified by co-immunoprecipitation assays and Western blot (WB) experiments detecting changes in cellular H3K9me3 levels following CCR7 ligand stimulation. The association between co-expression and patient clinical parameters, tumor burden, and progression-free survival (PFS) was evaluated through correlation analysis, Kaplan-Meier survival curves, and Cox regression analysis.</p><p><strong>Results: </strong>H3K9me3 expression was predominantly nuclear, whereas CCR7 was expressed on the cell membrane. Both markers were significantly upregulated in aggressive lymphomas and positively correlated with LDH, β2-microglobulin, and neutrophil percentage. An interaction between CCR7 and H3K9me3 could be demonstrated in that CCR7 ligand stimulation resulted in an upregulation of H3K9me3 expression. Enhanced H3K9me3 expression was associated with bone marrow infiltration. High expression of CCR7 was associated with poorer progression-free survival (PFS), whereas high expression of both CCR7 and H3K9me3 identified patients with the worst prognosis. Univariate and multivariate Cox regression analysis indicated that the combined expression was a potential prognostic biomarker for B-cell lymphoma.</p><p><strong>Conclusion: </strong>Co-elevated CCR7 and H3K9me3 expression defines a high-risk B-cell lymphoma subgroup with high tumor burden, bone marrow infiltration, and poor prognosis, highlighting their potential as biomarkers for risk stratification and candidate therapeutic targeting.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 1","pages":"25-39"},"PeriodicalIF":1.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluating cytokine storm syndromes: dysregulated host defense or contextual immune adaptation?","authors":"Abhishek Vijukumar, Hardik Kumar, Shilpa Debnath, Sourabh Kosey","doi":"10.32604/ecn.2026.078458","DOIUrl":"10.32604/ecn.2026.078458","url":null,"abstract":"<p><p>Cytokine storm syndromes have become a much-invoked concept to describe severe immunopathology in infectious, inflammatory, and iatrogenic diseases, but the concept is poorly defined and often mechanistically imprecise. High levels of systemic cytokines have often been viewed as indicators of immune dysfunction, and based on this notion, therapeutic interventions focused on general cytokine inhibition are proposed. Nevertheless, a growing number of clinical and experimental data dispute the notion that hypercytokinemia is necessarily pathological. The present paper reconsiders cytokine storm syndromes in the light of an evolutionary, systems-immunology model, and suggests that most cytokine amplification conditions are context-specific host defence programmes, however, not uniform maladaptations of immune regulation. Its major objective is to redefine the cytokine storm syndromes, which are no longer understood as a single, uniformly pathological situation, but as a spectrum of context-specific immune programmes. The paper reviews disease-specific phenotypes of cytokine storms in viral infections, bacterial sepsis, autoimmune diseases, and immune-based therapies, noting considerable variability in cytokine composition, kinetics of production, cytokine-producing cell frequency, and localization in tissues. It also explains how the temporal dynamics, host-specific conditions, and failure of counter-regulatory mechanisms define the difference between cytokine amplification as an adaptation or as a pathological condition. In addition, it considers the clinical consequences of such a refined framework and argues that exploring precision strategies need to consider immune context, disease stage, and signalling thresholds, as opposed to a general use of blocking cytokines. In conclusion, this review attempts to draw a line between adaptive cytokine amplification and maladaptive immunopathology by integrating the insights gained in evolutionary biology and systems immunology.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 1","pages":"13-24"},"PeriodicalIF":1.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propolis as a potential modulator of aryl hydrocarbon receptor signaling in inflammation.","authors":"Natália Alvarenga Borges, Larissa Manhães, Ludmilla Dias de Santana E Santana, Jessyca Sousa de Brito, Larissa Fonseca, Ludmila F M F Cardozo, Denise Mafra","doi":"10.32604/ecn.2026.0ECN78096","DOIUrl":"10.32604/ecn.2026.0ECN78096","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits antagonistic pleiotropy, mediating both protective and detrimental cellular effects depending on the ligand and context. AhR can be activated by a variety of endogenous and exogenous stimuli, including environmental pollutants, UVB radiation, heme, arachidonic acid metabolites, gut microbiota-derived compounds, and xenobiotics. Upon activation, AhR translocates to the nucleus, where it dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and binds to xenobiotic response elements, inducing the expression of genes involved in xenobiotic metabolism, oxidative stress responses, and inflammatory signaling. In addition to these classical pathways, AhR also modulates immune function by regulating cytokine networks, including IL-17, IL-22, and IL-10, which play key roles in barrier integrity and immune homeostasis. Bioactive dietary compounds, particularly polyphenols such as flavonoids, have emerged as potential modulators of AhR signaling. Propolis, a complex bee-derived product rich in flavonoids and other phenolic compounds, has demonstrated antioxidant and anti-inflammatory effects across multiple experimental models. However, the specific mechanisms through which propolis interacts with AhR signaling remain poorly understood. This mini-review summarizes current evidence on the potential role of propolis as an AhR modulator, discusses its implications for immune regulation, barrier function, and inflammation control, and highlights areas for future research.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"37 1","pages":"1-11"},"PeriodicalIF":1.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of interferon-stimulated gene 15 expression in the medulloblastoma context.","authors":"Eva G Palacios-Serrato, Karen Medina-Abreu, Gabriela Velasco-Loyden, Norma Angélica Lira-Rodríguez, Angeles C Tecalco-Cruz","doi":"10.1684/ecn.2025.0506","DOIUrl":"10.1684/ecn.2025.0506","url":null,"abstract":"<p><p>Interferon-stimulated gene 15 (ISG15) is a small ubiquitin-like protein that can be conjugated to its target proteins through an enzymatic cascade known as ISGylation, thereby altering their function. Elevated levels of free ISG15 (non-conjugated) and ISGylation are observed in several cancer types, including medulloblastoma (MB) a malignant pediatric cerebellar tumor categorized into four molecular subgroups: Wingless, Sonic Hedgehog, Subgroup 3 (G3), and Subgroup 4 (G4). However, ISG15 gene expression in MB remains unexplored. In this study, we evaluated the ISG15 protein levels, the expression of the ISG15 and ISGylation system, and interferon gamma signaling mediators in human MB samples to propose the role of ISG15 in this tumoral context. ISG15 expression in MB samples was comparatively analyzed against normal tissue using the Oncopression database. Expression levels were further assessed in various pediatric tumors within the Childhood Brain Tumor Tissue Consortium dataset via the University of Alabama at Birmingham Cancer Data Analysis Portal database. ISG15 protein abundance in MB samples was then evaluated via immunohistochemistry on a tumor tissue microarray. To broaden the analysis, ISG15 expression was profiled across multiple MB cell lines using the R2 Genomics Analysis and Visualization Platform. Finally, to determine clinical significance, the association between ISG15 expression and patient survival was assessed using Kaplan-Meier analysis. ISG15 expression was significantly lower in MB samples than in other pediatric tumors (p < 0.05) and normal tissue (p < 0.0001). Immunohistochemical analysis further confirmed a marked reduction in ISG15 protein abundance in MB samples compared to healthy tissue (p < 0.001). Elevated ISG15 levels correlated with improved survival outcomes in the G3 and G4 subgroups (p < 0.05). ISG15 is downregulated in MB tissues compared to controls. High ISG15 expression within the G3/G4 MB subgroups correlates with prolonged survival, suggesting a potential tumor-suppressive function. These results collectively indicate that ISG15 may serve as a valuable prognostic biomarker for G3/G4 MB patients.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"36 4","pages":"64-73"},"PeriodicalIF":1.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}