European Journal of Immunology最新文献

{"title":"Tumor-Expressed SPPL3 Supports Innate Antitumor Immune Responses","authors":"Tamara Verkerk,&nbsp;Antonius A. de Waard,&nbsp;Sofie J. I. Koomen,&nbsp;Jasper Sanders,&nbsp;Tineke Jorritsma,&nbsp;Anouk T. Pappot,&nbsp;Nordin D. Zandhuis,&nbsp;Tao Zhang,&nbsp;Manfred Wuhrer,&nbsp;Arie J. Hoogendijk,&nbsp;Floris P. J. van Alphen,&nbsp;Maartje van den Biggelaar,&nbsp;Hannes S. J. Stockinger,&nbsp;Klaas P. J. M. van Gisbergen,&nbsp;Robbert M. Spaapen,&nbsp;S. Marieke van Ham","doi":"10.1002/eji.202451129","DOIUrl":"10.1002/eji.202451129","url":null,"abstract":"<p>The development of an effective antitumor response relies on the synergistic actions of various immune cells that recognize tumor cells via distinct receptors. Tumors, however, often manipulate receptor–ligand interactions to evade recognition by the immune system. Recently, we highlighted the role of neolacto-series glycosphingolipids (nsGSLs), produced by the enzyme β1,3-<i>N</i>-acetylglucosaminyltransferase 5 (B3GNT5), in tumor immune escape. We previously demonstrated that loss of signal peptide peptidase like 3 (SPPL3), an inhibitor of B3GNT5, results in elevated levels of nsGSLs and impairs CD8 T cell activation. The impact of loss of SPPL3 and an elevated nsGSL profile in tumor cells on innate immune recognition remains to be elucidated. This study investigates the antitumor efficacy of neutrophils, NK cells, and γδ T cells on tumor cells lacking SPPL3. Our findings demonstrate that SPPL3-deficient target cells are less susceptible to trogocytosis by neutrophils and killing by NK cells and γδ T cells. Mechanistically, SPPL3 influences trogocytosis and γδ T cell-instigated killing through modulation of nsGSL expression, whereas SPPL3-mediated reduced killing by NK cells is nsGSL-independent. The nsGSL-dependent SPPL3 sensitivity depends on the proximity of surface receptor domains to the cell membrane and the affinity of receptor–ligand interactions as shown with various sets of defined antibodies. Thus, SPPL3 expression by tumor cells alters crosstalk with immune cells through the receptor–ligand interactome thereby driving escape not only from adaptive but also from innate immunity. These data underline the importance of investigating a potential synergism of GSL synthesis inhibitors with current immune cell-activating immunotherapies.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798899","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":"Issue Information: Eur. J. Immunol. 12'24","authors":"","doi":"10.1002/eji.202470122","DOIUrl":"https://doi.org/10.1002/eji.202470122","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868218","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":"High Extracellular K+ Skews T-Cell Differentiation Towards Tumour Promoting Th2 and Treg Subsets","authors":"Brandon Han Siang Wong,&nbsp;Zhi Sheng Poh,&nbsp;James Tan Chia Wei,&nbsp;Kottaiswamy Amuthavalli,&nbsp;Ying Swan Ho,&nbsp;Shuwen Chen,&nbsp;Shi Ya Mak,&nbsp;Xuezhi Bi,&nbsp;Richard D. Webster,&nbsp;Vishalkumar G. Shelat,&nbsp;K. George Chandy,&nbsp;Navin Kumar Verma","doi":"10.1002/eji.202451440","DOIUrl":"10.1002/eji.202451440","url":null,"abstract":"<p>Potassium ions (K⁺) released from dying necrotic tumour cells accumulate in the tumour microenvironment (TME) and increase the local K⁺ concentration to 50 mM (high-[K⁺]_e). Here, we demonstrate that high-[K⁺]_e decreases expression of the T-cell receptor subunits CD3ε and CD3ζ and co-stimulatory receptor CD28 and thereby dysregulates intracellular signal transduction cascades. High-[K⁺]_e also alters the metabolic profiles of T-cells, limiting the metabolism of glucose and glutamine, consistent with functional exhaustion. These changes skew T-cell differentiation, favouring Th2 and iT_reg subsets that promote tumour growth while restricting antitumour Th1 and Th17 subsets. Similar phenotypes were noted in T-cells present within the necrosis-prone core versus the outer zones of hepatocellular carcinoma (HCC)/colorectal carcinoma (CRC) tumours as analysed by GeoMx digital spatial profiling and flow-cytometry. Our results thus expand the understanding of the contribution of high-[K⁺]_e to the immunosuppressive milieu in the TME.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798898","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":"Cover Story: Eur. J. Immunol. 12'24","authors":"","doi":"10.1002/eji.202470121","DOIUrl":"https://doi.org/10.1002/eji.202470121","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":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202470121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868217","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":"Impressum","authors":"","doi":"10.1002/eji.202470123","DOIUrl":"https://doi.org/10.1002/eji.202470123","url":null,"abstract":"","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868328","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":"Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions","authors":"Orlando B. Giorgetti,&nbsp;Annette Haas-Assenbaum,&nbsp;Thomas Boehm","doi":"10.1002/eji.202451434","DOIUrl":"10.1002/eji.202451434","url":null,"abstract":"<p>The T-cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9-mediated mutagenesis of <i>Tcra</i> and <i>Tcrb</i> chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process illuminates the strong selective pressures that shape the repertoire of naïve T cells. Sequence analyses of the artificially diversified repertoires identify key amino acid residues in the CDR3 regions required for antigen recognition, indicating that artificial diversification of well-characterized TCR transgene sequences helps to reduce the complexities of learning the rules of antigen recognition.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764914","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":"Function and Spatial Organization of Tumor-Invasive Human γδ T Cells—What Do We Know?","authors":"Kilian Wistuba-Hamprecht,&nbsp;Hans-Heinrich Oberg,&nbsp;Daniela Wesch","doi":"10.1002/eji.202451075","DOIUrl":"10.1002/eji.202451075","url":null,"abstract":"<p>Human gammadelta (γ<i>δ</i>) T cells not only infiltrate or reside in healthy tissues but also enter solid cancers. A large body of evidence suggests that γ<i>δ</i> T cells can exert potent anti-tumor effects, although conflicting or unfavorable effects have been reported in some cancer entities. Infiltration patterns are key to understanding the complexity of the tumor microenvironment (TME) and its interplay with γ<i>δ</i> T cells. The limited data available describe different γ<i>δ</i> T cell subsets that are located in different areas around and within tumors. Tumor-infiltrating γ<i>δ</i> lymphocytes (γδ TIL) exert cytotoxicity, for example, via the CD95- or TRAIL-axis, produce high amounts of granzymes, and after their activation, tumor necrosis factor (TNF)-α or IFN-γ and express immune checkpoint receptors. Under certain conditions, γ<i>δ</i> T cell subsets can express low amounts of IL-17 and seem to contribute to immune regulation/suppression. A polarization of γ<i>δ</i> T cells can be influenced by the TME. Inflammatory cytokines, growth factors, or tumor promoters can suppress γ<i>δ</i> T cell functionality or even push them toward tumor promotion. To avoid this and to exploit the unique features of γ<i>δ</i> T cell–mediated anti-cancer and immune-orchestrating capabilities in future immune therapy approaches, a growing body of preclinical but also clinical studies can be observed.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764913","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":"IL1R2 Acts as a Negative Regulator of Monocyte Recruitment During Inflammation","authors":"Adeline Cros,&nbsp;Elodie Segura","doi":"10.1002/eji.202451468","DOIUrl":"10.1002/eji.202451468","url":null,"abstract":"<p>IL1-β plays a central role in inflammation but its biological action needs to be tightly controlled. Such negative regulation can be exerted by the decoy receptor IL1R2. However, IL1R2 biology in immune cells remains poorly characterized, in particular in monocytes. Using conditional deficient mice, we show that <i>Il1r2</i> deficiency in monocytes does not affect their steady-state life cycle but dysregulates their trafficking to inflamed tissues in models of peritonitis and neuro-inflammation. Mechanistically, we found that <i>Il1r2</i> deficiency in monocytes increases CCL2 secretion in the inflamed peritoneum, thereby amplifying monocyte recruitment from blood. In autoimmune neuro-inflammation, <i>Il1r2</i> deficiency in monocytes exacerbates disease severity. Our findings suggest that the specific action of IL1R2 in monocytes contributes to a feedback mechanism for fine-tuning the numbers of recruited monocytes during inflammation.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749522","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":"Distinct Requirements for CD4+ T Cell Help for Immune Responses Induced by mRNA and Adenovirus-Vector SARS-CoV-2 Vaccines","authors":"Lyn Yong,&nbsp;Claire Hutchings,&nbsp;Eleanor Barnes,&nbsp;Paul Klenerman,&nbsp;Nicholas M. Provine","doi":"10.1002/eji.202451142","DOIUrl":"10.1002/eji.202451142","url":null,"abstract":"<p>CD4⁺ T cells have been established as central orchestrators of cellular and humoral immune responses to infection or vaccination. However, the need for CD4⁺ T cell help to generate primary CD8⁺ T cell responses is variable depending on the infectious agent or vaccine and yet consistently required for the recall of CD8⁺ T cell memory responses or antibody responses. Given the deployment of new vaccine platforms such as nucleoside-modified mRNA vaccines, we sought to elucidate the requirement for CD4⁺ T cell help in the induction of cellular and antibody responses to mRNA and adenovirus (Ad)-vectored vaccines against SARS-CoV-2. Using antibody-mediated depletion of CD4⁺ T cells in a mouse immunization model, we observed that CD4⁺ T cell help was dispensable for both primary and secondary CD8⁺ T cell responses to the BNT162b2 and mRNA-1273 mRNA vaccines but required for the AZD1222 Ad-vectored vaccine. Nonetheless, CD4⁺ T cell help was needed by both mRNA and Ad-vectored vaccine platforms for the generation of antibodies, demonstrating the centrality of CD4⁺ T cells in vaccine-induced protective immunity against SARS-CoV-2. Ultimately, this highlights the shared and distinct regulation of humoral and cellular responses induced by these vaccine platforms.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737901","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":"Differential Characteristics on TCR Embedding Landscape Among Immune Checkpoint Blockade Responders Versus Non-Responders Against Non-Small Cell Lung Carcinoma","authors":"Peiling Tsou,&nbsp;Chang-Jiun Wu","doi":"10.1002/eji.202451374","DOIUrl":"10.1002/eji.202451374","url":null,"abstract":"<p>For each patient in the NSCLC cohort, TCR sequences were converted into numerical vectors using the TCR2Vec model and projected onto a 2D landscape. The aggregated fractions of anti-LAA TEGs per patient were calculated. ICB responders had over-represented anti-LAA TEGs compared to non-responders. \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":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737898","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}