Immunology & Cell Biology最新文献

{"title":"Phase 2 randomized controlled trial of seasonal influenza vaccine shows Advax^® delta inulin adjuvant accelerates the humoral anti-influenza response.","authors":"Lei Li, Yoshikazu Honda-Okubo, Varun Khanna, Dimitar Sajkov, Nikolai Petrovsky","doi":"10.1111/imcb.70050","DOIUrl":"https://doi.org/10.1111/imcb.70050","url":null,"abstract":"<p><p>Advax^® is a delta inulin polysaccharide adjuvant shown in animal models to enhance and accelerate influenza vaccine protection. A clinical trial was conducted in 109 healthy adult participants aged 18-70 years randomized to receive a single intramuscular seasonal trivalent influenza vaccine (TIV) alone or formulated with 5 or 10 mg Advax^® adjuvant to explore the effect of the adjuvant on the humoral immune response. The addition of Advax^® 10 mg to TIV accelerated the rise in serum influenza-specific antibodies, with this group exhibiting significantly higher increases in hemagglutinin inhibition (HAI) against 3 of the 3 vaccine serotypes at 7 days post-vaccination (7 dpv), 2 at 14 dpv and 1 at 21 dpv. By 7 dpv, the Advax 10-mg group achieved HAI seroprotection rates of 96.9% against H1N1, 100% against H3N2 and 46.9% against influenza B versus rates of 86.1%, 100% and 22.2%, respectively, for the TIV alone group. The Advax^®-adjuvanted groups demonstrated an increased frequency of non-silent CDR3 mutations in the B cell receptor heavy chain of peripheral blood IgG⁺ and IgM⁺ plasmablasts at 7 dpv, consistent with the adjuvant enhancing B cell affinity maturation in IgM⁺ and IgG⁺ plasmablasts independently of class switch recombination. The ability of Advax adjuvant to accelerate humoral responses against influenza could be advantageous during influenza outbreaks when time to protection is of the essence. Further studies are needed into the mechanisms whereby delta inulin accelerates vaccine immunity.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705894","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":"CD4⁺ tissue-resident memory T cells and their role in immunity.","authors":"Margarida Kirkby, Marc Veldhoen","doi":"10.1111/imcb.70052","DOIUrl":"https://doi.org/10.1111/imcb.70052","url":null,"abstract":"<p><p>CD4⁺ tissue-resident memory T (T_RM) cells are essential for immune protection in the lungs, providing rapid responses against respiratory pathogens. Unlike circulating memory T cells, CD4⁺ T_RM cells persist in the tissue parenchyma and possibly inducible lymphoid tissues, where they facilitate pathogen clearance through cytokine production and interactions with local immune cells. While CD8⁺ T_RM cells are well studied, the role of CD4⁺ T_RM cells in immunity remains less defined and is the focus of this review. Distinct subsets, based on the effector T_H1, T_H2, T_H17 and T follicular helper (T_FH)-like tissue-resident helper (T_RH) cells, contribute to antiviral, antibacterial, antifungal and vaccine-induced immunity. CD4⁺ T_RM cells play a key role in infections, enhancing immune responses and supporting antibody production. However, they are also implicated in chronic inflammation, allergies and fibrosis. Given their importance, vaccines aiming to elicit lung-resident CD4⁺ T_RM cells, particularly via mucosal delivery, have shown promise in inducing long-term protective immunity. Intranasal vaccination strategies, such as live-attenuated influenza virus and tuberculosis vaccines, have successfully generated CD4⁺ T_RM cells, highlighting their potential for respiratory pathogen control. In this review, we focus on CD4⁺ T_RM cells, their differentiation, maintenance and role, especially in the lungs.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705893","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":"Type I interferon: it's all about intracellular TLR4.","authors":"Harald Husebye","doi":"10.1111/imcb.70048","DOIUrl":"https://doi.org/10.1111/imcb.70048","url":null,"abstract":"<p><p>A recent extensive study from the Blumenthal research group has demonstrated that Toll-like receptor 4 (TLR4) signaling from the endosomes can be uncoupled from CD14-mediated endocytosis, revealing two distinct TLR4 signaling pathways. TLR4 was the first of the toll-like receptors to be discovered and one of the most studied.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606947","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":"PD-1 expressing islet-specific CD4⁺ T cells promote bystander tolerance and prevent autoimmunity.","authors":"Jeniffer D Loaiza Naranjo, Vivian Zhang, Rathna Ravichandran, Anne-Sophie Bergot, Ranjeny Thomas, Emma E Hamilton-Williams","doi":"10.1111/imcb.70044","DOIUrl":"https://doi.org/10.1111/imcb.70044","url":null,"abstract":"<p><p>Loss of T-cell tolerance to multiple islet antigens is a key feature of autoimmune type 1 diabetes. In this study, we investigated the requirement for programmed death 1 (PD-1) expression by CD4⁺ T cells in the maintenance of self-tolerance via bystander suppression of autoreactive CD8⁺ T cells using nonobese diabetic mice. We used CRISPR/Cas9 to selectively knockout PD-1 in islet antigen-specific BDC2.5 CD4⁺ T cells and observed the impact on bystander tolerance of 8.3 CD8⁺ T cells, specific for a different islet antigen. Loss of PD-1 promoted the proliferation, Th1-like effector-memory phenotype, islet infiltration and expression of cytotoxic markers by BDC2.5 cells. PD-1-deficient BDC2.5 cells were impaired in their regulation of 8.3 cells, which proliferated more, developed an effector-memory phenotype and increased expression of effector molecules. While antigen-presenting cell maturation and migration into the pancreatic lymph node were not impacted by loss of PD-1 expression from BDC2.5 cells, migration of BDC2.5 cells out of the lymph node was required for enhanced activation of the CD8⁺ T cells. Together, these events led to accelerated diabetes progression, suggesting that PD-1 expression by CD4⁺ T cells promotes a tolerogenic microenvironment and restraining autoreactive CD8⁺ T cells.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582738","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":"Addressing global health one Torque at a time.","authors":"Anvi Agarwal, Samiha Arulshankar","doi":"10.1111/imcb.70046","DOIUrl":"https://doi.org/10.1111/imcb.70046","url":null,"abstract":"<p><p>In this article, we discuss our experiences, as medical students, in raising awareness among fellow medical students about global health issues while providing insight into how other university students sharing these interests can set up similar initiatives.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551520","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":"Sketching T cell atlases in the single-cell era: challenges and recommendations.","authors":"Itana Bojović, António Gg Sousa, Sini Junttila, Laura L Elo","doi":"10.1111/imcb.70040","DOIUrl":"https://doi.org/10.1111/imcb.70040","url":null,"abstract":"<p><p>Recent advances in single-cell technologies have enabled the creation of comprehensive cell atlases, reference maps of various cell types within organisms. Here we specifically focus on T cell atlases, which offer a detailed catalog of the adaptive immune system at single-cell resolution. As such, they capture cellular diversity, functional states, and spatial dynamics across tissues, developmental stages, and disease conditions. Given the central role of T cells in orchestrating immune responses, their dysregulation underpins autoimmune disorders, cancer progression and failed immunotherapies. Therefore, a unified T cell atlas is critical for decoding such disease mechanisms, identifying therapeutic targets, and advancing personalized treatments. In this article, we explore the latest advances in T cell atlases, describing breakthroughs in multi-omics technologies, spatial profiling and computational frameworks that resolve transcriptional, epigenetic and proteomic heterogeneity. We also address persistent challenges and highlight strategies to address these gaps. Finally, we discuss emerging frontiers set to reshape our understanding of T cell dynamics in both health and diseases. Together, these insights underscore the transformative potential of T cell atlases in reconstructing precision immunology and accelerating therapeutic innovation.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525716","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":"Delta inulin alone or combined with CpG oligonucleotide enhances antibody-dependent influenza vaccine protection in mice and nonhuman primate newborns.","authors":"Isaac G Sakala, Yoshikazu Honda-Okubo, Nikolai Petrovsky","doi":"10.1111/imcb.70045","DOIUrl":"10.1111/imcb.70045","url":null,"abstract":"<p><p>Newborns represent over half of hospitalized pediatric influenza infection cases, with current influenza vaccines not effective in the first months of life. Advax^® (delta inulin) is a polysaccharide particle that targets DC-SIGN, whereas CpG55.2 is a potent murine and human toll-like receptor (TLR)-9 agonist. This study asked whether Advax or CpG alone, or combined, could enhance the protection of an inactivated influenza virus vaccine (IIV) in newborns. One-day-old mouse pups were immunized subcutaneously with a single dose of IIV alone or with Advax or Advax-CpG55.2 adjuvants and then, at 28 days of age, challenged intranasally with a lethal dose of influenza virus. While IIV alone or with CpG adjuvant provided minimal protection, Advax alone or combined with CpG55.2 induced enhanced serum anti-influenza IgM and IgG responses to IIV and protected the newborns against clinical disease. Protection induced by a single vaccine dose was highly durable and was still evident 6-9 months after a single neonatal immunization. Protection was lost in B-cell-deficient μMT pups but preserved in β2m knockout pups and in CD4⁺ and CD8⁺ T-cell-depleted pups, indicating the importance of intact humoral immunity to the enhanced protection. The neonatal benefits of Advax^® and Advax-CpG55.2 adjuvant were confirmed in newborn macaques, where they similarly enhanced serum anti-influenza antibody responses to IIV. This raises the possibility that Advax^® adjuvant alone or in combination with CpG55.2 may have utility in improving influenza vaccine protection in human newborns.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525715","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":"Th17 cells in cancer: plasticity-driven immunopathology and therapeutic opportunity.","authors":"Henry Sutanto, Mukti Citra Ningtyas, Betty Rachma, Laras Pratiwi, Deasy Fetarayani","doi":"10.1111/imcb.70043","DOIUrl":"https://doi.org/10.1111/imcb.70043","url":null,"abstract":"<p><p>T-helper 17 (Th17) cells, a subset of CD4⁺ T cells, are key players in mucosal immunity and inflammation, distinguished by their production of IL-17 and related cytokines. In the context of cancer, Th17 cells exhibit extraordinary plasticity-adapting their phenotype and function in response to tumor microenvironmental cues. This review explores how Th17 cells mediate paradoxical roles in tumor biology, promoting either tumor progression or antitumor immunity depending on molecular context. Protumorigenic functions include fostering angiogenesis, chronic inflammation and immune evasion through IL-17-driven recruitment of neutrophils and myeloid-derived suppressor cells. Conversely, Th17 cells can transition into IFNγ-producing Th1-like cells, enhancing cytotoxic T-cell responses and tumor rejection. Key modulators of this plasticity include cytokines (IL-23, IL-12, TGF-β), hypoxia, metabolic shifts and epigenetic reprogramming. We further examine how Th17 plasticity contributes to metastasis, therapy resistance and immune modulation via interactions with tumor-associated macrophages and regulatory T cells. Finally, the review highlights emerging therapeutic strategies that target Th17 pathways through cytokine blockade, metabolic intervention, RORγ modulation and adoptive cell therapy. Understanding Th17 plasticity provides critical insights into tumor immunology and offers novel avenues for cancer immunotherapy.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493279","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":"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}