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LAG3 checkpoint function and its mechanism of action in therapeutic targeting. LAG3检查点在靶向治疗中的作用机制
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-10-09 DOI: 10.1038/s41577-026-01359-2
Yong Jiang, Dario A A Vignali, Haopeng Wang
{"title":"LAG3 checkpoint function and its mechanism of action in therapeutic targeting.","authors":"Yong Jiang, Dario A A Vignali, Haopeng Wang","doi":"10.1038/s41577-026-01359-2","DOIUrl":"https://doi.org/10.1038/s41577-026-01359-2","url":null,"abstract":"<p><p>Lymphocyte activation gene 3 (LAG3) protein is a key immune inhibitory checkpoint receptor that suppresses T cell activation, proliferation and effector functions to maintain immune homeostasis and tolerance. In persistent pathological settings, chronic T cell receptor (TCR) signalling, together with sustained LAG3 signalling and other inhibitory receptor signalling, drives T cell dysfunction, highlighting LAG3 as a promising therapeutic target. However, more than 30 years after its discovery, the fundamental mechanisms governing LAG3 signalling and function remain incompletely defined. Elucidating LAG3 downstream signalling pathways and the mechanisms of action of LAG3-blocking antibodies is essential for identifying optimal clinical indications, developing predictive biomarkers, designing more effective LAG3-targeted therapeutics and maximizing clinical efficacy. Recent advances have revealed key molecular mechanisms, including constitutive tonic signalling, ligand-induced ubiquitination-dependent signalling switches and LAG3-TCR proximity-mediated suppression. In this Review, we comprehensively examine LAG3 signalling mechanisms, synthesize current understanding of its functional effect on T cells, discuss emerging therapeutics and their mechanisms of action, and evaluate biomarker strategies for patient selection. We conclude by highlighting key challenges and outlining future directions for LAG3-targeted immunotherapy in oncology and autoimmune disease.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148530","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}
引用次数: 0
Metastasizing cancer cells leave an immunogenic trail. 转移的癌细胞会留下免疫原痕迹。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-10-09 DOI: 10.1038/s41577-026-01366-3
Yvonne Bordon
{"title":"Metastasizing cancer cells leave an immunogenic trail.","authors":"Yvonne Bordon","doi":"10.1038/s41577-026-01366-3","DOIUrl":"https://doi.org/10.1038/s41577-026-01366-3","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149350","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}
引用次数: 0
A guide to B cell metabolism B细胞代谢指南
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2026-10-07 DOI: 10.1038/s41577-026-01355-6
Yavuz F. Yazicioglu,Glenn R. Bantug,Christoph Hess,Alexander J. Clarke
{"title":"A guide to B cell metabolism","authors":"Yavuz F. Yazicioglu,Glenn R. Bantug,Christoph Hess,Alexander J. Clarke","doi":"10.1038/s41577-026-01355-6","DOIUrl":"https://doi.org/10.1038/s41577-026-01355-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"4 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090239","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}
引用次数: 0
Sympathetic nerve activity primes susceptibility to autoimmune hair loss 交感神经活动导致自身免疫性脱发
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2026-10-05 DOI: 10.1038/s41577-026-01365-4
Kirsty Minton
{"title":"Sympathetic nerve activity primes susceptibility to autoimmune hair loss","authors":"Kirsty Minton","doi":"10.1038/s41577-026-01365-4","DOIUrl":"https://doi.org/10.1038/s41577-026-01365-4","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"1 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092130","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}
引用次数: 0
The effects of IFNγ on tissue physiology through structural cells. IFNγ通过结构细胞对组织生理的影响。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-29 DOI: 10.1038/s41577-026-01357-4
Irah L King, Bana Jabri, Amanda W Lund, Andrew Wang
{"title":"The effects of IFNγ on tissue physiology through structural cells.","authors":"Irah L King, Bana Jabri, Amanda W Lund, Andrew Wang","doi":"10.1038/s41577-026-01357-4","DOIUrl":"https://doi.org/10.1038/s41577-026-01357-4","url":null,"abstract":"<p><p>Interferon-γ (IFNγ) is classically defined by its potent ability to enhance the antimicrobial and tumour-killing activities of innate and adaptive immune cells, establishing it as an archetypal pro-inflammatory type 1 cytokine. However, as the most conserved of the interferons throughout evolution, it is possible that IFNγ may have a more fundamental physiological role beyond these immune functions. A rapidly growing body of literature now indicates that IFNγ acts extensively on non-haematopoietic, structural cells to regulate organ function, tissue homeostasis and context-dependent immune adaptation. These findings position IFNγ as a primary coordinator of diverse defence strategies, including host resistance, disease tolerance and trained immunity. In this Perspective, we examine how IFNγ signalling in non-haematopoietic cells complements or alters its canonical immune functions and argue that defining the context-specific and cell-specific actions of IFNγ is essential to inform therapeutic approaches targeting IFNγ that enhance immunity while preserving tissue function.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081551","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}
引用次数: 0
What the 'negative space' tells us about the immunology of multiple sclerosis. “负空间”告诉我们多发性硬化症的免疫学。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-28 DOI: 10.1038/s41577-026-01358-3
Max Kaufmann, Ralf Gold, Lars Fugger
{"title":"What the 'negative space' tells us about the immunology of multiple sclerosis.","authors":"Max Kaufmann, Ralf Gold, Lars Fugger","doi":"10.1038/s41577-026-01358-3","DOIUrl":"https://doi.org/10.1038/s41577-026-01358-3","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075262","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}
引用次数: 0
'Trained' sensory neurons drive allergic sensitization. “训练过的”感觉神经元驱动过敏致敏。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-28 DOI: 10.1038/s41577-026-01362-7
Kirsty Minton
{"title":"'Trained' sensory neurons drive allergic sensitization.","authors":"Kirsty Minton","doi":"10.1038/s41577-026-01362-7","DOIUrl":"https://doi.org/10.1038/s41577-026-01362-7","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075345","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}
引用次数: 0
Drugging the immune system: principles of immunopharmacology. 免疫系统用药：免疫药理学原理。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-28 DOI: 10.1038/s41577-026-01361-8
E John Wherry
{"title":"Drugging the immune system: principles of immunopharmacology.","authors":"E John Wherry","doi":"10.1038/s41577-026-01361-8","DOIUrl":"https://doi.org/10.1038/s41577-026-01361-8","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075278","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}
引用次数: 0
The next big questions in immunology 免疫学的下一个大问题
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-25 DOI: 10.1038/s41577-026-01353-8
{"title":"The next big questions in immunology","authors":"","doi":"10.1038/s41577-026-01353-8","DOIUrl":"10.1038/s41577-026-01353-8","url":null,"abstract":"As Nature Reviews Immunology marks its twenty-fifth anniversary, leading immunologists reflect on the questions, challenges and conditions that will shape the future of the field.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 10","pages":"707-708"},"PeriodicalIF":47.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41577-026-01353-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasticity of the infant immune system during the perinatal period. 围产期婴儿免疫系统的可塑性。
IF 47.1 1区 医学
Nature Reviews Immunology Pub Date : 2026-09-18 DOI: 10.1038/s41577-026-01354-7
Katrin Kierdorf, Markus Sperandio, Mathias W Hornef, Philipp Henneke
{"title":"Plasticity of the infant immune system during the perinatal period.","authors":"Katrin Kierdorf, Markus Sperandio, Mathias W Hornef, Philipp Henneke","doi":"10.1038/s41577-026-01354-7","DOIUrl":"https://doi.org/10.1038/s41577-026-01354-7","url":null,"abstract":"<p><p>All mammalian offspring, regardless of their developmental stage at birth, must survive the fetal-to-postnatal transition from intrauterine dependence on the mother to postnatal independence. A major challenge in this context is the allocation of limited energy resources between tissue development and growth, energy-intensive responses to infection and the establishment of host-microbial homeostasis. For a long time, it was thought that early-life immunity was immature and dysfunctional. It is only recently that we have begun to understand, at a mechanistic level, how perinatal immunity is tailored to mediate the transition to postnatal life. This adaptation requires a high degree of temporal plasticity, which integrates the developmental trajectories of immune cells, changes in barrier permeability, effects of the microbiota, the waning contribution of maternal immunity and effects of early-life antigen exposure. This Review analyses the existing evidence for perinatal immune plasticity and its underlying mechanisms and consequences, with a particular focus on myeloid cells and barrier immunity. It synthesizes models as to how this immune plasticity may be induced, maintained and therapeutically modulated, even beyond infancy, while highlighting interspecies differences and commonalities, as well as current research needs.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":""},"PeriodicalIF":47.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001704","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}
引用次数: 0
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