Nature Reviews Immunology最新文献

{"title":"Clock genes keep intestinal ILC3s ticking","authors":"Kirsty Minton","doi":"10.1038/s41577-025-01220-y","DOIUrl":"10.1038/s41577-025-01220-y","url":null,"abstract":"A study by Bhattarai et al. in Nature Immunology reports that ILC3-to-ILC1 plasticity in the gut is regulated by circadian clock proteins.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 10","pages":"708-708"},"PeriodicalIF":60.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915660","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":"Linking tumour angiogenesis and tumour immunity","authors":"Ashraf Ul Kabir, Madhav Subramanian, Yoojung Kwon, Kyunghee Choi","doi":"10.1038/s41577-025-01211-z","DOIUrl":"https://doi.org/10.1038/s41577-025-01211-z","url":null,"abstract":"<p>Immune checkpoint blockade therapy has revolutionized the treatment of metastatic and solid tumours, achieving durable responses in a subset of patients. However, most patients do not respond to immune checkpoint blockade, underscoring the critical need to better understand the determinants of therapeutic efficacy. A key obstacle to effective antitumour immune responses is the abnormal structure and function of tumour-associated blood vessels, which impede immune cell infiltration and contribute to the development of an immunosuppressive tumour microenvironment. Current research highlights the inverse correlation between angiogenesis and immune activity within the tumour microenvironment. In this Review, we discuss tumour angiogenesis in the context of tumour immunity, examining how this affects tumour progression and immunotherapy outcomes. We examine the molecular mechanisms underlying the crosstalk between angiogenesis and tumour immunity and discuss emerging anti-angiogenic regulators that hold potential for combination therapies. By integrating insights from preclinical and clinical studies, we outline future research directions to address current challenges and optimize cancer treatment strategies through combined anti-angiogenic and immunotherapeutic approaches.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"16 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840128","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":"Defects in antigen processing and presentation: mechanisms, immune evasion and implications for cancer vaccine development","authors":"Florian Huber, Michal Bassani-Sternberg","doi":"10.1038/s41577-025-01208-8","DOIUrl":"https://doi.org/10.1038/s41577-025-01208-8","url":null,"abstract":"<p>Human tumour cells express mutated and non-mutated proteins that can be processed and presented by these cells as peptides bound to human leukocyte antigen (HLA). Some of these peptides are recognized by cognate T cell receptors as ‘non-self’, leading to specific killing of tumour cells by T cells. This process is fundamental to the success of cancer immunotherapy, which exploits the ability of the immune system to eliminate transformed cells. Mutated antigens (neoantigens) have been implicated in the remarkable therapeutic efficacy of immune checkpoint inhibitors (ICIs), which boost endogenous antitumour immune responses. In recent years, the combination of ICIs with personalized cancer vaccines that target neoantigens and other tumour-specific antigens has emerged as a new therapeutic strategy. However, the robust immune pressure that ICIs exert on cancer cells inevitably amplifies the phenomenon of immune editing, which can allow cancer cells to develop resistance mechanisms that subvert surveillance by the immune system. Diminished antigenicity can be due to defects in the antigen processing and presentation machinery, such as <i>HLA-I/II</i> loss of heterozygosity and loss of functional β2-microglobulin. This poses a considerable challenge for combination therapies that include ICIs and for the design of cancer-specific vaccines.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"27 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797256","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":"Fifty years of monoclonals: the past, present and future of antibody therapeutics","authors":"Andrew C. Chan,&nbsp;Greg D. Martyn,&nbsp;Paul J. Carter","doi":"10.1038/s41577-025-01207-9","DOIUrl":"10.1038/s41577-025-01207-9","url":null,"abstract":"In 1975, Köhler and Milstein invented hybridoma technology for the generation of murine monoclonal antibodies with predetermined antigen-binding specificity. The transformative impact of monoclonal antibodies is demonstrated by their ubiquitous use as biomedical research reagents and the worldwide approval of at least 212 antibody therapeutics with tens of millions of patients treated to date. Advances in antibody technologies, such as humanization and robust methods for human antibody generation, mitigated the major limitations of murine antibodies as therapeutics. These technologies, combined with progress in biomanufacturing, helped to launch this modern era of antibody therapeutics. Beyond IgG, antibody therapeutics have blossomed into multiple alternative formats, including bispecific antibodies and antibody–drug conjugates. Additionally, antibody fragments have been developed as stand-alone therapeutics and to target cell therapies, notably chimeric antigen receptor T cells. These advances in antibody technologies, plus innovation enabling subcutaneous delivery, have improved the therapeutic benefits and convenience of antibody treatment for many patients. This concept is illustrated here by multiple generations of antibody therapeutics for human epidermal growth factor receptor 2 (HER2)+ cancers and B cell-targeted therapies for haematological cancers and immunological diseases. Finally, we opine briefly on some of the many promising future directions with antibody therapeutics, including the application of artificial intelligence for antibody identification and multi-parameter optimization. Fifty years ago, Köhler and Milstein introduced the world to hybridoma technology for the generation of monoclonal antibodies. Scientists have subsequently built upon this seminal discovery to develop antibody-based therapies for numerous diseases, with millions of patients benefiting from such drugs. To mark 50 years of monoclonal antibodies, this Review from Chan, Martyn and Carter provides an overview of how antibody engineering strategies have continued to improve antibody-based therapeutics, chiefly focusing on antibody-mediated targeting of B cells&nbsp;and also human epidermal growth factor receptor 2 (HER2)+ cancers. The authors also highlight the promise of emerging tools, including artificial intelligence, for development of the next generation of antibody-based therapeutics.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 10","pages":"745-765"},"PeriodicalIF":60.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792354","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":"Manipulation of the nucleotide pool in human, bacterial and plant immunity","authors":"Dina Hochhauser, Rotem Sorek","doi":"10.1038/s41577-025-01206-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01206-w","url":null,"abstract":"<p>The cell-autonomous innate immune system is responsible for sensing and mitigating viral infection at the level of individual cells. Many of the mechanisms used by the cell-autonomous innate immune system in eukaryotic cells are ancient and have evolutionary roots in bacterial systems that defend against phage infection. Studies from recent years have shown that modification of the free nucleotide pool is central to many of these conserved immune mechanisms. In this Review, we explain how immune pathways manipulate the available pool of nucleotides to deprive viruses of molecules essential for their replication, how immune proteins chemically modify nucleotides to generate immune signalling molecules, and how cell-autonomous innate immune mechanisms produce altered nucleotides that poison viral replication. We also discuss the mechanisms used by viruses to antagonize nucleotide-based immunity. Finally, we explore the evolutionary logic of using nucleotides as building blocks for immune responses.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"709 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719705","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":"Exercise induces metabolic changes in the gut microbiota that enhance anti-tumour T cell responses","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01217-7","DOIUrl":"10.1038/s41577-025-01217-7","url":null,"abstract":"Exercise promotes changes in the gut microbiota that enhance anti-tumour T cell responses.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 9","pages":"634-634"},"PeriodicalIF":60.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715334","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":"How stem cells respond to infection, inflammation and ageing.","authors":"Enzo Z Poirier","doi":"10.1038/s41577-025-01203-z","DOIUrl":"https://doi.org/10.1038/s41577-025-01203-z","url":null,"abstract":"Stem cells maintain tissue architecture by replacing differentiated cells at steady state and upon injury. Implementing this cornerstone role requires protection of stem cells from pathogens and from the toxic effects of immune system activation. However, the pro-inflammatory innate immune mechanisms that protect differentiated cells from infection are poorly functional in stem cells. Instead, stem cells employ other specific defence mechanisms, such as antiviral RNA interference. At steady state, the proliferation and differentiation of tissue stem cells is regulated by multiple cell types, including immune cells. Following sterile tissue injury or during infection, the immune response - in addition to controlling pathogens and clearing cell debris - orchestrates tissue repair by fine-tuning stem cell activity, through direct cell-cell contacts and via inflammatory mediators such as cytokines. There is thus stem-immune cross-talk that is fundamental to the maintenance of tissue homeostasis. Inflammageing, which is defined as the age-driven elevation of inflammation and is associated with an altered immune cell composition, profoundly affects this stem-immune cross-talk, impacting the ability to repair tissues and participating in ageing of the whole organism.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"14 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701339","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":"Live vaccine development through targeted protein degradation","authors":"Qisi Zhang,&nbsp;Longlong Si","doi":"10.1038/s41577-025-01212-y","DOIUrl":"10.1038/s41577-025-01212-y","url":null,"abstract":"In this Tools of the Trade article, Qisi Zhang and Longlong Si describe a method for generating live attenuated vaccines that involves targeting viruses to the host cells’ protein degradation machinery, which attenuates the virus within the host and also enhances viral antigen presentation.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 9","pages":"633-633"},"PeriodicalIF":60.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701340","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":"Mitochondrial proteins go public and novel interactions: insights from surfaceome mapping","authors":"Adam J. Grippin,&nbsp;Wen Jiang","doi":"10.1038/s41577-025-01216-8","DOIUrl":"10.1038/s41577-025-01216-8","url":null,"abstract":"A recent preprint by Floyd et al. presents the most comprehensive mapping to date of the human lymphocyte ‘surfaceome’.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 9","pages":"636-636"},"PeriodicalIF":60.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693220","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":"Uterine inflammation and lessons from large animal models of endometritis","authors":"Deborah M. Nash, Joanna L. Giles","doi":"10.1038/s41577-025-01200-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01200-2","url":null,"abstract":"<p>Uterine inflammation encompasses several conditions, including endometritis, which is a local innate immune response, usually to bacteria. Endometritis is an important veterinary and medical problem that can result in infertility and/or recurrent pregnancy loss. This Review aims to summarize animal models that can be used to uncover the immune pathways responsible for uterine inflammation and their value for screening novel, putative therapies. We discuss large animal models of endometritis, particularly the well-used bovine system and the value that may be added by further developing porcine systems. Animal cells and tissue explants can be ethically sourced, and these models can replace or reduce the need for live animal studies and overcome the practical issues of harvesting endometrial material from women. We explain how these models of endometritis show great potential for advancing our understanding of the immune dysfunction underlying susceptibility to the condition, and for early-stage drug discovery.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"27 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677305","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}