{"title":"Tumor Glycosylation: A Main Player in the Modulation of Immune Responses","authors":"Ernesto Rodriguez","doi":"10.1002/eji.202451318","DOIUrl":"https://doi.org/10.1002/eji.202451318","url":null,"abstract":"<p>Tumor immune escape refers to the process by which cancer cells evade detection and destruction by the immune system. Glycosylation, a post-translational modification that is altered in almost all cancer types, plays a crucial role in this process by modulating immune responses. This review examines our current understanding of how aberrant tumor glycosylation contributes to a tolerogenic microenvironment, focusing on specific glycosylation signatures—fucosylation, truncated O-glycans, and sialylation—and the immune receptors involved. Additionally, the clinical significance of tumor glycosylation is discussed, emphasizing its potential in developing novel therapeutic approaches aimed at improving immune system recognition and targeting of cancer cells. The review underscores the importance of ongoing research in this area to identify effective strategies for countering tumor immune escape and enhancing the efficacy of cancer treatments.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595274","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}
Huu Thanh Le, Carola Venturini, Alicia Fajardo Lubian, Bethany Bowring, Jonathan Iredell, Jacob George, Golo Ahlenstiel, Scott A. Read
{"title":"Differences in Phage Recognition and Immunogenicity Contribute to Divergent Human Immune Responses to Escherichia coli and Klebsiella pneumoniae Phages","authors":"Huu Thanh Le, Carola Venturini, Alicia Fajardo Lubian, Bethany Bowring, Jonathan Iredell, Jacob George, Golo Ahlenstiel, Scott A. Read","doi":"10.1002/eji.202451543","DOIUrl":"https://doi.org/10.1002/eji.202451543","url":null,"abstract":"<p>Bacteriophages (phages) are emerging as a viable adjunct to antibiotics for the treatment of multidrug-resistant (MDR) bacterial infections. While intravenous phage therapy has proven successful in many cases, clinical outcomes remain uncertain due to a limited understanding of host response to phages. In this study, we conducted a comprehensive examination of the interaction between clinical-grade phages used to treat MDR <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> infections, and human peripheral blood immune cells. Using whole transcriptome as well as proteomic approaches, we identified a strong inflammatory response to <i>E. coli</i> phage vB_EcoM-JIPh_Ec70 (herein, JIPh_Ec70) that was absent upon exposure to <i>K. pneumoniae</i> phage JIPh_Kp127. We confirmed that JIPh_Ec70's DNA recognition by the STING pathway was principally responsible for the activation of NF-kB and the subsequent inflammatory response. We further show that monocytes and neutrophils play a dominant role in phage uptake, primarily through complement-mediated phagocytosis. Significant differences in complement-mediated phagocytosis of JIPh_Kp127 and JIPh_Ec70 were observed, suggesting that reduced recognition, phagocytosis, and immunogenicity all contribute to the significantly decreased response to JIPh_Kp127. Our findings contribute to the progress of our understanding of the innate immune response to therapeutic phages and offer potential insights into how to improve the safety and effectiveness of phage therapy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595276","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}
Marleen Y. van Smoorenburg, Ester B. M. Remmerswaal, Celia Segui-Perez, John L. van Hamme, Karin Strijbis, Teunis B. H. Geijtenbeek
{"title":"Vaginal Prevotella timonensis Bacteria Enhance HIV-1 Uptake and Differentially Affect Transmission by Distinct Primary Dendritic Cell Subsets","authors":"Marleen Y. van Smoorenburg, Ester B. M. Remmerswaal, Celia Segui-Perez, John L. van Hamme, Karin Strijbis, Teunis B. H. Geijtenbeek","doi":"10.1002/eji.202451192","DOIUrl":"https://doi.org/10.1002/eji.202451192","url":null,"abstract":"<p>Young females are at high risk of acquiring HIV-1 infections and an imbalance in the vaginal microbiome enhances susceptibility to HIV-1 infection. More insights into the underlying mechanisms could open up new strategies to prevent HIV-1 acquisition and dissemination. Here, we investigated the effect of anaerobic bacteria associated with bacterial vaginosis (BV) on HIV-1 transmission by two distinct dendritic cell (DC) subsets, that is, inflammatory monocyte-derived DCs (moDCs) and primary CD1c<sup>+</sup> DCs. Notably, in contrast to other BV-associated microbiota, <i>Prevotella timonensis</i> enhanced uptake of HIV-1 by both moDCs and CD1c<sup>+</sup> DCs and the increased uptake was independent of cellular HIV-1 (co-)receptors. Imaging flow cytometry analyses showed that HIV-1 did not co-localise with <i>P. timonensis</i> but was internalized into tetraspanin-positive compartments known to be involved in HIV-1 transmission. <i>P. timonensis</i> bacteria enhanced HIV-1 transmission by CD1c<sup>+</sup> DCs, but not by moDCs, and the enhanced transmission was independent of viral infection. Our study strongly suggests that mucosal DC subsets have distinct functions in BV-associated HIV-1 susceptibility, and underscores the importance of early diagnosis and targeted treatment of vaginal dysbiosis to reduce the risk of HIV-1 acquisition.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595548","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":"A Critical Oversight in Immunology Research: The Prevalence of Complement Deficiencies in Mouse Models","authors":"África González-Fernández","doi":"10.1002/eji.202451678","DOIUrl":"https://doi.org/10.1002/eji.202451678","url":null,"abstract":"<div>\u0000 \u0000 <p>The complement system is a crucial component of the innate immune response, playing a vital role in defending the body against pathogens and maintaining homeostasis. This complex network of proteins acts as a first line of defense, enhancing the ability of antibodies and phagocytic cells to clear microbes and damaged cells. It also participates in inflammation processes and leukocyte recruitment. However, findings regarding a common mutation in the complement component C5 in mouse strains have raised concerns about the validity of numerous studies in immunology, including infectious diseases, inflammatory, autoimmune disorders, and cancer research.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595275","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}
{"title":"Cover Story: Eur. J. Immunol. 3'25","authors":"","doi":"10.1002/eji.202570031","DOIUrl":"https://doi.org/10.1002/eji.202570031","url":null,"abstract":"<p>Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.\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 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202570031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595153","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}
Laura Ceglarek, Ramona Gerhards, Vinicius Boldrini, Christian Wichmann, Anneli Peters, Edgar Meinl
{"title":"BTK-Inhibition Enhances TLR-7-Mediated Interferon-Alpha Production in pDCs by Blocking the Inhibitory BDCA-2 Pathway","authors":"Laura Ceglarek, Ramona Gerhards, Vinicius Boldrini, Christian Wichmann, Anneli Peters, Edgar Meinl","doi":"10.1002/eji.202450985","DOIUrl":"https://doi.org/10.1002/eji.202450985","url":null,"abstract":"<p>In pDCs, BTK-inhibition (BTKi) blocks the IFN-α production via TLR-9, but not via TLR-7. Upon TLR-7 stimulation, BTKi enhances the production of IFN-α by blocking the inhibitory BDCA-2 pathway. This might explain partially the failure of BTKi in SLE and is of interest for BTKi trials in multiple sclerosis.\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 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202450985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475708","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}
Rose Shalah, Manal Marzouk, Enas Hallumi, Naama Klopstock, Deborah Yablonski
{"title":"Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T-Cell Adaptor Gads","authors":"Rose Shalah, Manal Marzouk, Enas Hallumi, Naama Klopstock, Deborah Yablonski","doi":"10.1002/eji.202451000","DOIUrl":"https://doi.org/10.1002/eji.202451000","url":null,"abstract":"<p>Thymocyte β-selection and positive-selection depend on TCR signaling via the immune adaptors SLP-76 and LAT. Gads bridges the recruitment of SLP-76 to LAT, yet is not required for the maturation of single positive (SP) thymocytes. To illuminate this paradox, we performed tamoxifen-induced ablation of Gads (Gads<sup>iKO</sup>), accompanied by the expression of tdTomato, and compared the development of Gads-expressing (Tom<sup>−</sup>) and Gads-ablated (Tom<sup>+</sup>) thymocytes within the same mouse. Gads<sup>iKO</sup> (Tom<sup>+</sup>) thymocytes exhibited impaired β- and positive-selection, yet δ-selection was not affected. While susceptible to apoptosis ex vivo, the marked accumulation of self-MHC nonresponding (CD5<sup>−</sup>) Gads<sup>iKO</sup> DP thymocytes suggested the possibility of impaired death by neglect in situ. Further supporting this notion, Gads<sup>iKO</sup> CD5<sup>lo</sup> DP thymocytes exhibited reduced apoptosis in situ and reduced CD8-induced apoptosis ex vivo. Most Gads<sup>iKO</sup> CD4 SP thymocytes were positively selected, yet a distinct population of unselected (CD5<sup>−</sup> TCRβ<sup>neg/low</sup> CCR7<sup>lo</sup> CD24<sup>hi</sup>) CD4 SP thymocytes was seen only in the absence of Gads. This unselected population did not include Treg or TCRγδ subsets; rather, it encompassed CD44<sup>lo</sup> CD25<sup>+</sup> cells, resembling pre-β-selection thymocytes. Our results suggest that Gads promotes passage through key TCR-driven developmental checkpoints while repressing the progression of unselected DN and DP thymocytes.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475718","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":"VSTM1/SIRL-1: An Inhibitory Pattern Recognition Receptor Regulating Myeloid Cells","authors":"Maaike Koops, Linde Meyaard","doi":"10.1002/eji.202451465","DOIUrl":"https://doi.org/10.1002/eji.202451465","url":null,"abstract":"<p>Innate immune cells express a plethora of inhibitory receptors, many of which recognize molecular patterns. An appropriate balance between signaling via activating and inhibitory pattern recognition receptors is important for a proper immune response while preventing immunopathology. V-set and transmembrane domain containing 1 (VSTM1), also known as signal inhibitory receptor on leukocytes-1 (SIRL-1), is an inhibitory receptor expressed on myeloid cells. VSTM1 can modulate the function of myeloid cells, by inhibiting reactive oxygen species and neutrophil extracellular trap formation. VSTM1 recognizes shared molecular patterns both from endogenous and microbial origin, defining it as an inhibitory pattern recognition receptor. VSTM1 is involved in various pathological conditions, including autoimmune disorders and cancer, and its restricted expression on myeloid cells highlights its potential as a specific therapeutic target. This review summarizes the characteristics and function of VSTM1 in health and disease.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475716","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":"Trametinib Suppresses the Stimulated T Cells Through G1 Arrest and Apoptosis","authors":"Toshimasa Nakao, Takero Shindo, Hideki Takakura, Takumi Narita, Yukako Ise-Nakao, Saeko Akiyama, Yosuke Iizumi, Shogen Boku, Motoki Watanabe, Toshiyuki Sakai, Seiichi Shimizu, Masaki Yamada, Yoshihiro Sowa, Michihiro Mutoh","doi":"10.1002/eji.202350667","DOIUrl":"https://doi.org/10.1002/eji.202350667","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of efficient immunosuppressants may bring significant benefits to patients after organ/stem transplantation and those with allergies or autoimmune diseases. MEK inhibitors were originally developed as anticancer reagents, but recent reports have suggested that they may have the potential to be immunosuppressants. Trametinib is a first-in-class MEK inhibitor. Here, we examined the effects of trametinib on the immune system and revealed its mechanism. Trametinib suppressed both CD4 and CD8 T-cell proliferation and activated T cells, which expressed CD25 and TIM3, in a dose-dependent manner in vitro. Trametinib also suppressed T cell-related cytokine secretion in a dose-dependent manner. Notably, trametinib suppressed T cell proliferation through the induction of G1 arrest and apoptosis in stimulated T cells. In addition, trametinib induced regulatory T cells (Tregs). We confirmed that low concentrations of trametinib (1 and 10 nM) were not toxic toward splenic naïve T cells and normal mouse liver cells. In this study, we demonstrated whether trametinib suppressed CD4 and CD8 T cell proliferation by inducing G1 arrest and apoptosis along with suppression of cytokine secretion.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475717","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}