{"title":"Skin Treg cells set the tone for neuronal activation.","authors":"Kirsty Minton","doi":"10.1038/s41577-025-01232-8","DOIUrl":"https://doi.org/10.1038/s41577-025-01232-8","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"1 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulators of CD8+ T cell exhaustion.","authors":"Qinli Sun,Chen Dong","doi":"10.1038/s41577-025-01221-x","DOIUrl":"https://doi.org/10.1038/s41577-025-01221-x","url":null,"abstract":"T cell exhaustion is an adaptive and distinct cell fate that emerges in response to persistent antigen stimulation, primarily in chronic infections and cancer. It is characterized by a progressive loss of effector functions and sustained expression of multiple inhibitory receptors. Progression to T cell exhaustion is driven by persistent antigen stimulation through the T cell receptor and is modulated by signals from co-stimulatory and inhibitory molecules as well as by microenvironmental factors such as cytokines, metabolites and neuronal factors. These extrinsic cellular factors reshape the T cell transcriptome, epigenome and metabolism towards a state of exhaustion through critical intrinsic cell regulators. In this Review, we summarize our current understanding of the regulators involved in T cell exhaustion, highlighting their roles in directing the fates and functionalities of distinct exhausted T cell subsets and how they may be harnessed for the development of improved immunotherapies against cancer and chronic infections.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"88 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.","authors":"Francesca Fallarino,Christian U Blank","doi":"10.1038/s41577-025-01222-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01222-w","url":null,"abstract":"Immunotherapy has become a fourth pillar of cancer therapy, alongside surgery, radiotherapy and chemotherapy. Cancer immunotherapy seems to be most effective in the context of low but not negligible tumour burden, thus in the neoadjuvant setting before curative intent surgery. Indeed, in the case of macroscopic stage III melanoma, a decade of clinical and translational research has led to conclusive evidence that neoadjuvant immunotherapy should be the clinical standard of care, although its adoption in different regions of the world is still ongoing. In this Perspective, we discuss the lessons learnt from neoadjuvant immunotherapy trials in melanoma and where the field is heading next. In the coming years, we believe that biomarker-driven personalization of the therapy, a deeper understanding of the role of immune education, and the ability to uncouple toxicity from efficacy will make neoadjuvant cancer immunotherapy safer and more effective, not only for melanoma but also for other types of cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"11 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clearing the hurdles for CAR-T cell treatment.","authors":"Rayne H Rouce","doi":"10.1038/s41577-025-01228-4","DOIUrl":"https://doi.org/10.1038/s41577-025-01228-4","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"61 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung Bum Park, Paul Zimmer-Harwood, T. Jake Liang
{"title":"Targets of protective immunity and opportunities in hepatitis C virus vaccine development","authors":"Seung Bum Park, Paul Zimmer-Harwood, T. Jake Liang","doi":"10.1038/s41577-025-01215-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01215-9","url":null,"abstract":"<p>Hepatitis C virus (HCV) remains a serious global health burden that affects nearly 50 million people worldwide. Despite the availability of highly effective direct-acting antiviral drugs, the lack of an effective HCV vaccine hinders control and elimination worldwide, wherein new infections and overall prevalence remain high. HCV vaccine development faces challenges including high genetic diversity of the virus, unclear correlates of protective immunity, and lack of robust in vivo models for vaccine testing. Despite these obstacles, the landscape of HCV vaccine development is rapidly evolving. Innovative strategies, including subunit, virus-like particle, viral vector, DNA and RNA vaccines, show promising results, and controlled human infection models offer a unique, albeit ethically complex, opportunity to accelerate vaccine development. Collaborative efforts among academia, industry, governmental agencies and regulatory bodies are crucial for optimizing vaccine strategies, overcoming current challenges and effecting advances towards global HCV elimination through vaccination.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"35 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation","authors":"Loïc Dupré, Irinka Castanon, Kaan Boztug","doi":"10.1038/s41577-025-01214-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01214-w","url":null,"abstract":"<p>Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell–cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is highlighted by the discovery of inborn errors of immunity (IEIs) that are caused by defects in individual actin-regulatory proteins, resulting in immune-related actinopathies. In addition to susceptibility to infection, these often present with a vast array of autoimmune and autoinflammatory manifestations. Here, we review the role of actin subnetworks in the activation and function of lymphoid and myeloid cells. We focus on the mechanisms by which actin defects result in aberrant lymphocyte function, including dysregulation of T cell- and B cell-mediated tolerance and biased cytokine production, which can result in autoimmunity. We also highlight the relationship between actin defects and inflammasome activation and other pathomechanisms in myeloid cells as the underlying cause of autoinflammation. Finally, we discuss future avenues for research and therapeutic intervention based on a molecular understanding of immune-related actinopathies.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"14 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic control of innate-like T cells","authors":"Thomas Riffelmacher, Mitchell Kronenberg","doi":"10.1038/s41577-025-01219-5","DOIUrl":"https://doi.org/10.1038/s41577-025-01219-5","url":null,"abstract":"<p>Immunometabolism, the intersection of cellular metabolism and immune function, has revolutionized our understanding of T cell biology. Changes in cellular metabolism help guide the development of thymocytes and the transition of T cells from naive to effector, memory and tissue-resident states. Innate-like T cells are a unique group of T cells with special characteristics. They respond rapidly, reside mainly in tissues and express T cell receptors with limited diversity that recognize non-peptide antigens. This group includes invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and some populations of γδ T cells. Different subsets of innate-like T cells rely on specific metabolic pathways that influence their differentiation and function and distinguish them from conventional CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Although there are differences between innate-like T cell types, they share metabolic and functional features. In this Review, we highlight recent research in this emerging field. Understanding how metabolic programmes differ between innate-like T cells and other T cells may open opportunities for tailoring innate-like T cell responses and adoptive T cell therapies for use in cancer, metabolic and autoimmune diseases.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"15 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Klaus Früh, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael, Louis J. Picker
{"title":"Targeting MHC-E as a new strategy for vaccines and immunotherapeutics","authors":"Klaus Früh, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael, Louis J. Picker","doi":"10.1038/s41577-025-01218-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01218-6","url":null,"abstract":"<p>MHC-E is a highly conserved, non-polymorphic MHC protein that engages inhibitory and activating receptors on natural killer (NK) cells and T cells and can also present antigens to T cell receptors. NK cell responses driven by activating receptor interactions with MHC-E are implicated in controlling chronic viral infections and cancer. Immunotherapeutic targeting of interactions between MHC-E and inhibitory receptors to increase the activation of NK cells and T cells shows promise in improving antitumour immune responses. Furthermore, MHC-E-restricted CD8<sup>+</sup> T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8<sup>+</sup> T cells restricted by classical MHC class I or class II molecules. The ability of MHC-E to regulate or mediate both innate and adaptive immune responses independently of the MHC haplotype of an individual raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer. Although the therapeutic exploitation of MHC-E is still in its infancy, recent advances in the understanding of MHC-E biology show enormous potential, as described in this Review.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"32 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"B cell trailblazers connect EBV to MS","authors":"Lucy Bird","doi":"10.1038/s41577-025-01224-8","DOIUrl":"10.1038/s41577-025-01224-8","url":null,"abstract":"B cells that expand following infection with EBV can colonize the brain, where they recruit activated T cells that have potential to cause neuronal damage, thereby providing a mechanism to explain the link between EBV and increased MS risk.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 10","pages":"707-707"},"PeriodicalIF":60.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulatory KIR+CD8+ T cells in pregnancy","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01225-7","DOIUrl":"10.1038/s41577-025-01225-7","url":null,"abstract":"Populations of regulatory KIR+CD8+ T cells expand during pregnancy and can promote maternal tolerance to the developing fetus.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 10","pages":"709-709"},"PeriodicalIF":60.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}