{"title":"Machine Learning Reassessment of Serum Immune Factors Shows No Unique Immune Profiles Linked to Disease Outcomes in SARS-CoV-2-infected Patients at Hospital Admittance","authors":"Stefania Rossi, Imerio Capone, Enrico Cabri, Anna Giabelli, Ilaria Rossoni, Giulia Romagnoli, Stefano M. Santini, Cinzia Marcantonio, Roberto Giuseppetti, Umbertina Villano, Roberto Bruni, Anna R. Ciccaglione, Federica Frasca, Alessandra d'Auria, Ginevra Bugani, Gabriella d'Ettorre, Guido Antonelli, Carolina Scagnolari, Maddalena Fratelli, Lucia Gabriele","doi":"10.1002/eji.70001","DOIUrl":"https://doi.org/10.1002/eji.70001","url":null,"abstract":"<p>The complex pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves a hyperinflammatory state with excessive cytokine production, leading to an influenza-like syndrome that may need emergency care. The severity of SARS-CoV-2 varies widely, and collective serum immune factors, evaluated in emergency care patients, have not been shown to correlate with disease progression. We applied a machine learning approach to reassess and define serum immune profiles that could align with clinical laboratory parameters and predict disease outcomes in patients with respiratory virus infections, including those with SARS-CoV-2, seeking emergency care. Sixty-two plasma immune molecules, in a cohort of 67 symptomatic SARS-CoV-2, were analyzed for correlation with antibodies (Abs) to spike (S) and nucleocapsid (N) proteins, as well as with clinical laboratory parameters, to identify early indicators of disease prognosis at hospital admission. This approach allowed us to analyze and cluster unlabeled datasets, delineating three distinct serum immune signatures. Two showed significant and opposite modulations, correlating with poorer disease outcomes, while most patients with moderate disease displayed modest immune factor dysregulation. This highlights the complexity of immune responses in the severity of diseases caused by highly respiratory pathogenic virus like SARS-CoV-2, emphasizing the importance of evaluating overall immune imbalance rather than focusing on a few dysregulated factors.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Platelet-Based Nanotechnology Improves Cancer Immunotherapy","authors":"Yanlin Lv, Guanghui Ma","doi":"10.1002/eji.70017","DOIUrl":"https://doi.org/10.1002/eji.70017","url":null,"abstract":"<p>Cancer immunotherapy is a cornerstone of precision medicine, yet its efficacy is often hampered by the immunosuppressive and heterogeneous microenvironment of solid tumors. Biomimetic nanodelivery systems have emerged as promising tools to enhance therapeutic outcomes while minimizing off-target effects. Among these, platelet (PLT)-based systems offer unique advantages, including prolonged circulation, immune evasion, and tumor-targeting capabilities. Of particular value is their ability to localize to sites of injury, which is a feature that nanocarriers cannot achieve. This review explores the multifaceted role of platelets in tumor development and metastasis, highlighting their bidirectional interactions with tumors. It further discusses the application of PLT-based nanotechnology in cancer immunotherapy, emphasizing recent advancements in immune regulation, targeted therapy, and clinical translation. We also address the challenges and considerations in developing PLT-based platforms, outlining future directions for their optimization in cancer treatment.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Klaudia Maria Grieger, Valerie Schröder, Susann Dehmel, Vanessa Neuhaus, Dirk Schaudien, Maximillian Fuchs, Helena Linge, Alexander Wagner, Ulf Kulik, Benjamin Gundert, Heiko Aselmann, Armin Braun, Christina Hesse, Katherina Sewald
{"title":"Ex Vivo Modeling and Pharmacological Modulation of Tissue Immune Responses in Inflammatory Bowel Disease Using Precision-Cut Intestinal Slices","authors":"Klaudia Maria Grieger, Valerie Schröder, Susann Dehmel, Vanessa Neuhaus, Dirk Schaudien, Maximillian Fuchs, Helena Linge, Alexander Wagner, Ulf Kulik, Benjamin Gundert, Heiko Aselmann, Armin Braun, Christina Hesse, Katherina Sewald","doi":"10.1002/eji.70013","DOIUrl":"https://doi.org/10.1002/eji.70013","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) affects approximately 5 million people worldwide, causing chronic inflammation and increased mortality. Despite advances in therapy, the underlying immune mechanisms remain poorly understood, highlighting the need for human-immunocompetent models to enhance translational research. This study aimed to investigate local immune responses using precision-cut intestinal slices (PCIS) from IBD patients and evaluate immunomodulatory treatment directly in patient tissue ex vivo. PCIS from ileal resections of IBD and non-IBD patients were stimulated with Concanavalin A (ConA) or lipopolysaccharide (LPS). Histological analysis of IBD-derived PCIS showed villus atrophy, infiltration of lymphocytes and macrophages, and RNA analysis revealed upregulation of IL-17 and interferon signaling pathways. LPS- and ConA-induced functional immune responses in the tissue, with IBD tissue exhibiting increased levels of specific cytokines compared with non-IBD tissue, including IL-17F and IL-21 after ConA-stimulation, and IL-22 as well as ENA-78 following LPS-stimulation. Pimecrolimus treatment led to a marked reduction in the release of IL-2, IL-17A, and IFN-γ, and inhibited the IBD supernatant-induced reduction in transepithelial electrical resistance. Our data provide the first in-depth characterization of local tissue immune responses in human PCIS, highlighting the potential of this model to study disease-specific immune activity and evaluate pharmacological interventions ex vivo.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Vasilyeva, Olivia Makinson, Cynthia Chan, Maria Park, Colin O'Dwyer, Ayad Ali, Abrar Ul Haq Khan, Christiano Tanese de Souza, Mohamed S. Hasim, Sara Asif, Reem Kurdieh, John Abou-Hamad, Edward Yakubovich, Jonathan Hodgins, Paul Al Haddad, Giuseppe Pietropaolo, Julija Mazej, Hobin Seo, Qiutong Huang, Sarah Nersesian, Damien Chay, Nicolas Jacquelot, David Cook, Seung-Hwan Lee, Giuseppe Sciumè, Stephen Waggoner, Michele Ardolino, Marie Marotel
{"title":"LAG3 Marks Activated but Hyporesponsive NK Cells","authors":"Valeria Vasilyeva, Olivia Makinson, Cynthia Chan, Maria Park, Colin O'Dwyer, Ayad Ali, Abrar Ul Haq Khan, Christiano Tanese de Souza, Mohamed S. Hasim, Sara Asif, Reem Kurdieh, John Abou-Hamad, Edward Yakubovich, Jonathan Hodgins, Paul Al Haddad, Giuseppe Pietropaolo, Julija Mazej, Hobin Seo, Qiutong Huang, Sarah Nersesian, Damien Chay, Nicolas Jacquelot, David Cook, Seung-Hwan Lee, Giuseppe Sciumè, Stephen Waggoner, Michele Ardolino, Marie Marotel","doi":"10.1002/eji.70009","DOIUrl":"https://doi.org/10.1002/eji.70009","url":null,"abstract":"<p>NK cells are critical for immunosurveillance, yet become dysfunctional when chronically stimulated by virally infected or cancerous cells. This phenomenon is similar to T cell exhaustion but less characterized, limiting therapeutic interventions. As shown for T cells, NK cells often display an increased expression of immune checkpoint proteins (ICP) following chronic stimulation, and ICP blockade therapies are currently being explored for several cancer types, with remarkable patient benefits. Nevertheless, the nature of ICP expression in NK cells is still poorly documented. In this study, we aimed to identify the conditions that lead to and the phenotype of immune checkpoint LAG3-expressing NK cells. Using various experimental models, we found that LAG3 is expressed by murine NK cells upon activation in different contexts, including in response to cancer and acute viral infections. LAG3 marks a subset of immature, proliferating, and activated cells, which, despite activation, have a reduced capacity to respond to a broad range of stimuli. Further characterization also revealed that LAG3+ NK cells exhibit a transcriptional signature similar to that of exhausted CD8+ T cells. Taken together, our results support the use of LAG3 as a marker of dysfunctional NK cells across diverse chronic and acute inflammatory conditions.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Self-Antigens Select B Cells: A New Perspective on B Cell Selection and Function","authors":"Mike Aoun, Rikard Holmdahl","doi":"10.1002/eji.202451720","DOIUrl":"https://doi.org/10.1002/eji.202451720","url":null,"abstract":"<p>The adaptive immune system is shaped by self-recognition, creating a paradox where autoreactivity is essential for immune regulation, yet implicated in autoimmune diseases. Traditionally, B cell selection in the bone marrow (BM) has been viewed through the lens of negative selection, eliminating potentially harmful clones. Emerging evidence challenges this perspective, revealing a subset of B suppressor cells (Bsup) that actively regulate immune homeostasis. Unlike conventional negative selection, C1-specific Bsup cells, which recognize collagen type II (Col2), engage Col2-specific regulatory T cells (Tregs) to suppress inflammation in healthy individuals. This suggests that Bsup play a role in both peripheral and central tolerance, akin to Tregs. However, the molecular mechanisms governing Bsup selection, differentiation, and function remain unknown. Understanding how Bsup distinguish homeostatic from pathogenic autoreactivity could transform autoimmune disease treatment, shifting the focus from eliminating autoreactive B cells to harnessing their regulatory potential for precision immunotherapy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margaux Gerbaux, Frederik Staels, Mathijs Willemsen, Julika Neumann, Leoni Bücken, Lize Van Meerbeeck, Willem Roosens, Adrian Liston, Stéphanie Humblet-Baron, Rik Schrijvers
{"title":"Homozygosity for the Common IL23R R381Q Variant Associates with Increased Susceptibility to Chronic Mucocutaneous Candidiasis","authors":"Margaux Gerbaux, Frederik Staels, Mathijs Willemsen, Julika Neumann, Leoni Bücken, Lize Van Meerbeeck, Willem Roosens, Adrian Liston, Stéphanie Humblet-Baron, Rik Schrijvers","doi":"10.1002/eji.70002","DOIUrl":"https://doi.org/10.1002/eji.70002","url":null,"abstract":"<p>Chronic mucocutaneous candidiasis can be caused by an Inborn Error of Immunity, especially those affecting TH-17 / IL-17 responses. Through in-depth immunophenotyping and functional assays, we reveal the association between homozygous carriage of the common p.R381Q IL-23R genetic variant and increased candidiasis susceptibility, relying on disrupted IL-23-mediated IL-17 immunity.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Marlies Duda, Manuela Gehring, Bettina Wedi
{"title":"Activation of the Complement/Lectin Pathway, Angiopoietin/Tie-2/VEGF-System, Cytokines and Chemokines in Different Angioedema Subtypes","authors":"Katharina Marlies Duda, Manuela Gehring, Bettina Wedi","doi":"10.1002/eji.70010","DOIUrl":"https://doi.org/10.1002/eji.70010","url":null,"abstract":"<p>The precise molecular mechanisms underlying angioedema attacks in cases of C1-inhibitor-deficient hereditary angioedema (C1-INH-HAE), angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), and mast cell-/histamine-mediated angioedema (Hist-AE) are not well understood. These attacks may involve immune and inflammatory mechanisms. We compared serum biomarkers indicating vascular integrity, leakage, angiogenesis, coagulation, and inflammation. During an attack-free period, we assessed 34 markers simultaneously using multi- and/or singleplex ELISA in 25 patients with C1-INH-HAE, 17 with ACEi-AE, 25 with Hist-AE, and 23 healthy controls. Differential blood counts, C1-INH-HAE-specific laboratory parameters, and recently developed assays addressing early complement and lectin pathways were included. The results revealed significant differences, as well as some similarities. Tie-2, VEGFs, C1s/C1INHc appear to play a role in all AE types regardless of whether they are bradykinin- or histamine-mediated. Furthermore, evidence was found for a role of IL-17, eosinophil, and neutrophil chemotactic factors, and the activation of these granulocytes was found. MASP-1/C1-INHc indicated early activation of the lectin pathway in ACEi-AE and HistAE, but not in C1-INH-HAE. C1s/C1-INHc and MASP-1/C1INHc ratio was able to discriminate C1-INH-HAE from controls and the other AE types. Future investigations in C1-INH-HAE, ACEi-AE, and Hist-AE should not only focus on complement activation but also the interaction with granulocytes.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation","authors":"Shagnik Chattopadhyay, Sayantee Hazra, Biswajit Biswas, Ritobrata Goswami","doi":"10.1002/eji.202451752","DOIUrl":"https://doi.org/10.1002/eji.202451752","url":null,"abstract":"<div>\u0000 \u0000 <p>CD4+ T helper cells are involved in multiple biological processes ranging from pathogen clearance to immune tolerance. Differentiation of CD4+ T cells into varied subsets is dependent on transcription factors, cytokines, micronutrients, and epigenetic modifications. Here, we report the molecular mechanisms imparted by the homeobox transcription factor HOXB4 in modulating Th2 and Th9 cell differentiation. We found that <i>Hoxb4</i> induction in T helper cells was TGF-β-dependent. In Th9 cells, HOXB4 overexpression significantly increased IL-9 secretion, while in Th2 cells, HOXB4 could alter only IL-10 secretion among other type 2 cytokines. Promoter activity analyses revealed that HOXB4 was able to transactivate the <i>Il9</i> and <i>Il10</i> proximal promoters, while the <i>Il4</i> and <i>Il13</i> promoters were differentially modulated. We observed that HOXB4 could physically interact with the transcription factor PU.1 but not GATA3, and directly bind PU.1 response element on the DNA in Th9 cells. The recruitment of HOXB4 was found to be significantly increased in regulatory regions including cECR and CNS1 (<i>Il9</i> promoter). Collectively, our findings suggest that HOXB4 works downstream of the TGF-β signalling pathway, associates with PU.1, binds the regulatory regions, and distinctly regulates both Th2 and Th9 cell differentiation.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksandra Dyczko, Beatriz F. Côrte-Real, Ibrahim Hamad, Ralf A. Linker, Markus Kleinewietfeld
{"title":"Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration","authors":"Aleksandra Dyczko, Beatriz F. Côrte-Real, Ibrahim Hamad, Ralf A. Linker, Markus Kleinewietfeld","doi":"10.1002/eji.202451260","DOIUrl":"https://doi.org/10.1002/eji.202451260","url":null,"abstract":"<div>\u0000 \u0000 <p>Regulatory FOXP3<sup>+</sup> T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). Several studies have indicated that Treg mitochondrial fitness is crucial for maintaining their stability and suppressive activity with an emphasis on complex-III of the electron transport chain (ETC). Dysfunctional Tregs isolated from patients with autoimmunity like multiple sclerosis (MS) show diminished mitochondrial respiration and the induction of a T helper (Th)1-like phenotype, characterized by increased production of interferon (IFN)-γ. Teriflunomide reduces the proliferation of activated T and B lymphocytes by inhibition of de novo pyrimidine synthesis, providing therapy for patients with autoimmune diseases. Recent data demonstrated that teriflunomide further inhibited complex-III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex-III activity for Tregs, we therefore thought to investigate with this study the effects of teriflunomide on immunometabolism and function in human Tregs. Interestingly, teriflunomide impaired the mitochondrial function of human Tregs and further induced a Th1-like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro- versus anti-inflammatory T cell subsets, indicating the need for further detailed evaluation.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aoise O'Neill, Norashikin Zakaria, Hannah Egan, Oliver Treacy, Aisling M. Hogan, Michael O'Dwyer, Sean O. Hynes, Aideen E. Ryan
{"title":"The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment","authors":"Aoise O'Neill, Norashikin Zakaria, Hannah Egan, Oliver Treacy, Aisling M. Hogan, Michael O'Dwyer, Sean O. Hynes, Aideen E. Ryan","doi":"10.1002/eji.70000","DOIUrl":"https://doi.org/10.1002/eji.70000","url":null,"abstract":"<p>The tumour microenvironment (TME) comprises a complex interplay of tumour cells, nonmalignant cells (including endothelial, immune, and stromal cells), and secreted factors within the extracellular matrix (ECM). Immunosuppression within the TME significantly hinders the efficacy of cancer immunotherapies. Stromal-rich TMEs, characterised by an abundance of mesenchymal stromal cells (MSCs) and cancer-associated fibroblasts (CAFs), are particularly immunosuppressive and associated with poor responses to conventional and immune-based therapies. Glycans, carbohydrate structures on cell surfaces, are dynamically regulated during tumourigenesis and mediate crucial cell–cell communications through receptor–ligand interactions. Sialylation, the addition of sialic acids to glycans, forms sialoglycans that can engage inhibitory Siglec receptors expressed on immune cells and promote immunosuppressive signalling. Emerging evidence implicates aberrant sialylation in the TME as a key driver of immunosuppression. More recently, sialylation of stromal cells in the TME has been shown to suppress anti-tumor immunity. This review explores the role of sialylation within stromal-rich, immunosuppressive TMEs, focusing on how specific sialic acid/Siglec interactions dictate innate and adaptive immune responses. We discuss the potential of targeting glycoimmune checkpoints to overcome stromal-mediated resistance and enhance anti-tumour immunity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}