Immunology & Cell Biology最新文献

{"title":"Characterization of ex vivo expanded natural killer cells for cancer immunotherapy.","authors":"Jin Young Min, Tae Kyung Ko, Hye Min Kim, Hae Won Jung, Cha Ok Yim, Eun Hee Han","doi":"10.1111/imcb.70038","DOIUrl":"https://doi.org/10.1111/imcb.70038","url":null,"abstract":"<p><p>In this study, we employed a coculture system to expand natural killer (NK) cells ex vivo from healthy donors and patients with breast cancer and investigated their surface marker expression. We further analyzed the activation markers of primary expanded NK cells on Day 13 using cytokine arrays and dimensionality reduction techniques. Cytokine profiles were observed on Days 0, 6 and 13 (TS-NK). To validate the anticancer activity of the expanded NK cells, we conducted lactate dehydrogenase assays against the hematologic cancer cell line K562 using cells from 10 donors (five patients with cancer and five healthy individuals). Additionally, we examined the antibody-dependent cellular cytotoxicity (ADCC) of differentiated NK cells cocultured with SK-BR-3 cells in the presence of the HER2-targeting monoclonal antibodies, trastuzumab and pertuzumab. Our findings demonstrate the stable expansion of NK cells from donor peripheral blood mononuclear cells and their potent anticancer effects and ADCC against both hematologic and solid tumors, highlighting their potential as a versatile therapeutic approach in oncology.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324007","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":"ICB Special Feature: Highlights of 2024","authors":"Joanne H Reed","doi":"10.1111/imcb.70041","DOIUrl":"10.1111/imcb.70041","url":null,"abstract":"<p>This Special Feature brings you the “Highlights of 2024”, a collection of short articles to bring you up to date on major advances in immunology research published in 2024. Each highlight article summarizes the key papers that drove new discoveries in a specific area of immunology. Pankhurst and Linterman<span>¹</span> highlight the latest discoveries in the germinal center response and new opportunities for the development of more effective vaccines and immunotherapies. Flaman <i>et al</i>.<span>²</span> focus on key studies that provide critical insights into the development, differentiation, and longevity of antibody secreting cells in health and disease. In Lee and Reed,<span>³</span> we review recent findings on age-associated B cells, the discovery of their transcriptional regulator, and the evidence for a pathogenic role in autoimmune disease. Valentini <i>et al</i>.<span>⁴</span> discuss metabolic pathways that alter regulatory T-cell function and differentiation and their potential as therapeutic targets in inflammatory niches, tumors and autoimmune disease. McEwan <i>et al</i>.<span>⁵</span> update us on the growing evidence that the most important risk gene for Alzheimer's disease, the apolipoprotein E variant, APOE4 drives immune dysregulation causing neuroinflammation and neurodegeneration. Eberl<span>⁶</span> summarizes the role of γδ T cells in tissues during sepsis while referring to 58 Taylor Swift song titles—<i>how many can you find</i>? 2024 was also a big year for innate lymphoid cells (ILC), with Shen <i>et al</i>.<span>⁷</span> discussing tissue-specific roles for ILC3, highlighting metabolic and checkpoint molecules as targets for immunotherapy. Shajan <i>et al</i>.<span>⁸</span> summarizes the critical signaling pathways, epigenetic modifications and cytokines-regulating natural killer (NK) cell function and survival. Bourel <i>et al</i>.<span>⁹</span> review the latest strategies to enhance NK cell cytotoxicity and memory for cell-based cancer therapy. Finally, Jose <i>et al</i>.<span>¹⁰</span> discuss advances and clinical trials for antibody–drug conjugates, which combine monoclonal antibody specificity with cytotoxic agents to selectively deliver potent drugs to tumor cells.</p><p>Whether you are reliving some of 2024's key findings in your field or learning about the major advances in another area, this Special Feature will get you up to date and ready for another exciting year or immunology.</p><p>The author declares no conflicts of interest.</p><p><b>Joanne H Reed:</b> Conceptualization; writing – original draft; writing – review and editing.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 6","pages":"490-491"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting glutamine metabolism in CD4⁺ T-cell-mediated autoimmune diseases.","authors":"Zheng Li, ZeHong Su, ZhiMin Wu, LvHeng He, PingPing Hu, GaoJian Lian","doi":"10.1111/imcb.70042","DOIUrl":"https://doi.org/10.1111/imcb.70042","url":null,"abstract":"<p><p>CD4⁺ T cells play a vital role in the occurrence and development of autoimmune diseases (AID). The differentiation direction and function of CD4⁺ T cells are both regulated by metabolic reprogramming, which differs across various CD4⁺ T subsets. Glutamine (Gln), as an immunoregulatory nutrient, not only provides bioenergy and biosynthesis for the differentiation and effector function of CD4⁺ T cells but also regulates intracellular redox conditions and produces metabolic intermediates that are used for epigenetic modification of effector cell genes. Here, we review the metabolic characteristics of Gln in CD4⁺ T cells and its regulatory effects on CD4⁺ T-cell differentiation and function. We also summarize potential targets on Gln metabolism for AID therapy, including Gln transporters, Gls1, GSH synthesis and epigenetic modification. However, the primary challenge remains how to achieve cell type-specific metabolic inhibition in vivo. Therefore, future research should focus on developing selective and effective therapeutic agents that modulate Gln metabolism while minimizing cytotoxicity for AID treatment.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324009","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":"Serum proteomic and metabolomic analyses from patients with IBD identify biological pathways associated with treatment success with anti-integrin therapy.","authors":"John D Rioux, Gabrielle Boucher, Anik Forest, Bertrand Bouchard, Lise Coderre, Caroline Daneault, Isabelle Robillard Frayne, Julie Thompson Legault, Alain Bitton, Ashwin Ananthakrishnan, Sylvie Lesage, Ramnik J Xavier, Christine Des Rosiers","doi":"10.1111/imcb.70039","DOIUrl":"10.1111/imcb.70039","url":null,"abstract":"<p><p>Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise from an imbalance between its epithelial, immune and microbial components. It has been shown that biological differences (e.g. genetic, epigenetic, microbial, environmental) exist between patients with IBD. It is also known that there is important heterogeneity in the response to therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking). The aim of this study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as vedolizumab. We performed targeted analyses of > 150 proteins and metabolites, and nontargeted analyses of > 1100 lipid entities in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (week 14 samples). We detected that the baseline levels of multiple serum cytokines, amino acids, acylcarnitines and triglycerides were different between responders and nonresponders to treatment with vedolizumab. We also noted changes in serum analytes between baseline and week 14 samples that were different between these two groups of patients. Many of these serum analytes are markers of biological pathways that are involved in the activation, proliferation and metabolism of pro-inflammatory cells. This study provides support for the hypothesis that biological differences between individuals not only impact the risk to develop IBD and IBD-related clinical phenotypes but also an IBD patient's likelihood of responding to a biological therapy.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281823","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":"Interferon signaling in type-2 dendritic cells supports TH2 and T follicular helper fates in response to allergens","authors":"Greta R Webb,&nbsp;Kerry L Hilligan,&nbsp;Sam I Old,&nbsp;Shiau-Choot Tang,&nbsp;Olivier Lamiable,&nbsp;Franca Ronchese","doi":"10.1111/imcb.70035","DOIUrl":"10.1111/imcb.70035","url":null,"abstract":"<p>Type-2 dendritic cells (DC2s) are essential for the initiation of type-2 immune responses, but the signaling pathways involved in allergen sensing, DC activation and instruction of CD4⁺ T cell differentiation into T_H2 cells remain unclear. Previous studies demonstrated a type-I interferon (IFN-I) signature in skin DC2s following immunization with non-viable larvae of the helminth <i>Nippostrongylus brasiliensis</i> (<i>Nb</i>), house dust mite (HDM) or <i>Schistosoma</i> egg antigen (SEA). Here we show that conditional loss of IFNAR1 signaling in CD11c⁺ DCs significantly impaired T_H2 effector and T follicular helper (TFH) CD4⁺ T cell responses to <i>Nb. In vivo</i> proliferation experiments demonstrated reduced numbers of highly divided CD4⁺ T cells in IFNAR1^∆CD11c mice compared to IFNAR1^WT, with similar proportions of GATA3^hi T_H2 cells within the divided populations indicating that IFNAR1 signaling in DCs was supporting T cell priming and expansion rather than GATA3^hi differentiation. By contrast, TFHs were present in lower frequencies in IFNAR1^∆CD11c mice compared to IFNAR1^WT, suggesting that IFN-I signaling in DCs is necessary for allergen-specific TFH differentiation. Characterization of the DC2 compartment by flow cytometry and bulk RNAseq demonstrated lower numbers of <i>Nb</i>⁺ DC2s in draining lymph nodes (dLN) and reduced expression of genes involved in DC2 motility, focal adhesion, and antigen processing, while expression of costimulatory molecules and cell survival and apoptosis pathway scores were similar. Therefore, IFN-I conditioning of skin DC2s is necessary for their effective priming of CD4⁺ T_H2 responses to allergens and likely acts through the additive effects of multiple IFN-I-regulated pathways in DC2s.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 6","pages":"578-594"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214494","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":"Highlights of 2024: unleashing the power of NK cells—cancer's worst nightmare","authors":"Capucine Bourel,&nbsp;Fernando Souza-Fonseca-Guimaraes,&nbsp;Sylvie Lesage","doi":"10.1111/imcb.70037","DOIUrl":"10.1111/imcb.70037","url":null,"abstract":"<p>In this article for the Highlights of 2024 Series, we discuss strategies to enhance NK cell-based cancer therapies. These include (1) cytokine expression on bacterial membranes to boost NK cell activation in tumors, (2) optimizing CAR-NK cell manufacturing for improved efficacy, (3) using CRISPR-Cas9 to identify and target inhibitory genes, and (4) using tetraspecific engagers to enhance cytotoxicity and cytokine memory-like NK cells strengthening anti-tumor responses. This year's progress holds much promise for cancer treatments exploiting NK cells.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 6","pages":"526-529"},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platforms for studying cell-cell recognition by immune cells.","authors":"Jordan Kramer, P Anton van der Merwe, Omer Dushek","doi":"10.1111/imcb.70036","DOIUrl":"https://doi.org/10.1111/imcb.70036","url":null,"abstract":"<p><p>Immune cells interact directly with other cells and make decisions by integrating information from many different receptor-ligand interactions at these cell-cell interfaces. Since they encounter a huge variety of normal and abnormal cells, they experience many different combinations and concentrations of ligands. Understanding immune responses therefore requires platforms that enable ligands to be easily manipulated. We review and compare the available platforms, focusing on T-cell recognition. Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow. In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility. A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties. By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172333","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":"Highlights of 2024: Advances in Germinal Centers","authors":"Theresa E Pankhurst,&nbsp;Michelle A Linterman","doi":"10.1111/imcb.70032","DOIUrl":"10.1111/imcb.70032","url":null,"abstract":"<p>In this article for the Highlights of 2024 series, we review the latest advances in the biology of the germinal center response. These discoveries provide key insights into germinal center function and dysregulation, uncovering new opportunities for the development of more effective vaccines.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 6","pages":"492-495"},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of T follicular regulatory cells: exploring their expanding ontogeny and differentiation pathways.","authors":"Maria Miguel Cavaco, Pedro Gaspar, Rui do Amaral Vieira, Filipa Ribeiro, Luis Graca","doi":"10.1111/imcb.70026","DOIUrl":"https://doi.org/10.1111/imcb.70026","url":null,"abstract":"<p><p>T follicular regulatory (Tfr) cells have emerged as key mediators in controlling germinal center (GC) responses, preventing excessive immune activation and preserving self-tolerance. Initially thought to originate solely from thymic T regulatory cells (tTregs), recent findings reveal a more complex picture involving multiple differentiation pathways contributing to their heterogeneity. The natural route of differentiation comprises the most abundant subset, which originates from tTregs and retains the expression of CD25 (CD25⁺ nTfr), before transitioning into a more mature CD25-negative state within the GC (CD25^- nTfr). Conversely, the induced route (iTfr) includes Tfr cells that arise alongside nTfr cells but originate from peripheral Tregs or CD25-expressing Tfh cells, in addition to a late-GC subset (late Tfr) that emerges through the expression of FoxP3 by Tfh cells. The identification of circulating Tfr cells (cTfr) in peripheral blood, especially useful for studying immune dysregulation in humans, provides insights into their systemic roles and potential as biomarkers for immune dysfunction in different clinical scenarios. While it becomes evident that Tfr cells exhibit a heterogeneous nature, a deeper understanding of their distinct subsets could pave the way for targeted immunomodulatory strategies in the development of novel vaccines and therapeutics. This review provides a comprehensive overview of Tfr cell diversity, exploring their ontogeny, functional roles, and impact on immune homeostasis and disease.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092405","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":"A trial-blazer in clinical research.","authors":"Alex Johnston, Arti Medhavy, Suzanne Elliott, Danielle I Stanisic","doi":"10.1111/imcb.70034","DOIUrl":"https://doi.org/10.1111/imcb.70034","url":null,"abstract":"<p><p>Founded in 2005, Gallipoli Medical Research (GMR) is a leading independent medical research institute located in Greenslopes, Brisbane, Queensland. GMR strives to enrich and restore lives through pioneering medical research that transcends the laboratory to deliver meaningful and tangible real-world solutions. In 2006, GMR launched its clinical trials program at one of Australia's largest private hospitals, with the focus on advancing healthcare through innovative treatments and emerging therapies, with a particular focus on oncology, liver, and respiratory diseases. Dr Suzanne Elliott is the Associate Director of Clinical Trials at GMR. Here, Dr Elliott discusses her transition from laboratory-based research into the clinical trial industry and shares her insight, advice, and pioneering contributions to industry, government, and the clinical trial research landscape across her diverse 30-year career.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101278","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}