Pub Date : 2025-09-08DOI: 10.1038/s41577-025-01219-5
Thomas Riffelmacher, Mitchell Kronenberg
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+ and CD8+ 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. Functional and metabolic properties of innate-like T cells — namely, iNKT cells, MAIT cells and some γδ T cells — differ from those of conventional T cells. This Review describes how metabolic pathways support innate-like T cell properties such as acquisition of effector capability in the thymus, rapid responsiveness, tissue persistence, antigen adaptation and functional flexibility.
{"title":"Metabolic control of innate-like T cells","authors":"Thomas Riffelmacher, Mitchell Kronenberg","doi":"10.1038/s41577-025-01219-5","DOIUrl":"10.1038/s41577-025-01219-5","url":null,"abstract":"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+ and CD8+ 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. Functional and metabolic properties of innate-like T cells — namely, iNKT cells, MAIT cells and some γδ T cells — differ from those of conventional T cells. This Review describes how metabolic pathways support innate-like T cell properties such as acquisition of effector capability in the thymus, rapid responsiveness, tissue persistence, antigen adaptation and functional flexibility.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 1","pages":"67-82"},"PeriodicalIF":60.9,"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}
Pub Date : 2025-09-03DOI: 10.1038/s41577-025-01218-6
Klaus Früh, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael, Louis J. Picker
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+ T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8+ 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. The dual nature of non-polymorphic MHC-E as a ligand for innate receptors and as an antigen-presenting protein raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer that are independent of the MHC haplotype of an individual.
{"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":"10.1038/s41577-025-01218-6","url":null,"abstract":"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+ T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8+ 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. The dual nature of non-polymorphic MHC-E as a ligand for innate receptors and as an antigen-presenting protein raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer that are independent of the MHC haplotype of an individual.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 1","pages":"52-66"},"PeriodicalIF":60.9,"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}
Pub Date : 2025-09-01DOI: 10.1038/s41577-025-01224-8
Lucy Bird
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.
{"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}
Pub Date : 2025-09-01DOI: 10.1038/s41577-025-01225-7
Yvonne Bordon
Populations of regulatory KIR+CD8+ T cells expand during pregnancy and can promote maternal tolerance to the developing fetus.
调节性KIR+CD8+ T细胞群体在怀孕期间扩增，可以促进母体对发育中的胎儿的耐受性。
{"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}
{"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}
Pub Date : 2025-08-14DOI: 10.1038/s41577-025-01211-z
Ashraf Ul Kabir, Madhav Subramanian, Yoojung Kwon, Kyunghee Choi
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. Tumour-associated blood vessels are abnormal in structure and function, and this can limit immune cell infiltration into tumours and contribute to the immunosuppressive tumour microenvironment. This Review highlights how tumour angiogenesis impacts antitumour immunity and explains why combining anti-angiogenic strategies with immunotherapies could improve clinical outcomes for patients with cancer.
{"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":"10.1038/s41577-025-01211-z","url":null,"abstract":"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. Tumour-associated blood vessels are abnormal in structure and function, and this can limit immune cell infiltration into tumours and contribute to the immunosuppressive tumour microenvironment. This Review highlights how tumour angiogenesis impacts antitumour immunity and explains why combining anti-angiogenic strategies with immunotherapies could improve clinical outcomes for patients with cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 1","pages":"35-51"},"PeriodicalIF":60.9,"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}
Pub Date : 2025-08-08DOI: 10.1038/s41577-025-01208-8
Florian Huber, Michal Bassani-Sternberg
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 HLA-I/II 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. Effective tumour-specific T cell immunity — and the success of cancer immunotherapies — relies on the presentation of antigens via human leukocyte antigen (HLA) molecules. In this Review, Bassani-Sternberg and Huber explore recent advances in understanding the repertoire of tumour-specific antigens, as well as how disruptions in antigen processing and presentation contribute to immune evasion and resistance to immune checkpoint blockade. The authors also highlight how these insights can inform the design of personalized neoantigen-based vaccines and combination therapies aimed at outpacing tumour immunoediting.
{"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":"10.1038/s41577-025-01208-8","url":null,"abstract":"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 HLA-I/II 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. Effective tumour-specific T cell immunity — and the success of cancer immunotherapies — relies on the presentation of antigens via human leukocyte antigen (HLA) molecules. In this Review, Bassani-Sternberg and Huber explore recent advances in understanding the repertoire of tumour-specific antigens, as well as how disruptions in antigen processing and presentation contribute to immune evasion and resistance to immune checkpoint blockade. The authors also highlight how these insights can inform the design of personalized neoantigen-based vaccines and combination therapies aimed at outpacing tumour immunoediting.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 1","pages":"23-34"},"PeriodicalIF":60.9,"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}
Pub Date : 2025-08-07DOI: 10.1038/s41577-025-01207-9
Andrew C. Chan, Greg D. Martyn, Paul J. Carter
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 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.
{"title":"Fifty years of monoclonals: the past, present and future of antibody therapeutics","authors":"Andrew C. Chan, Greg D. Martyn, 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 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}
Pub Date : 2025-07-29DOI: 10.1038/s41577-025-01206-w
Dina Hochhauser, Rotem Sorek
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. Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nucleotide pool to block viral replication and produce immune signalling molecules.
{"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":"10.1038/s41577-025-01206-w","url":null,"abstract":"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. Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nucleotide pool to block viral replication and produce immune signalling molecules.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 1","pages":"7-22"},"PeriodicalIF":60.9,"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}
Pub Date : 2025-07-28DOI: 10.1038/s41577-025-01217-7
Yvonne Bordon
Exercise promotes changes in the gut microbiota that enhance anti-tumour T cell responses.
运动促进肠道微生物群的变化，增强抗肿瘤T细胞反应。
{"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}
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