{"title":"T cell exhaustion: early or late in tumour progression?","authors":"Lorenzo Galluzzi","doi":"10.1038/s41577-025-01158-1","DOIUrl":"10.1038/s41577-025-01158-1","url":null,"abstract":"Chronic antigen exposure underlies the stepwise acquisition of a terminally dysfunctional state by CD8+ T cells, commonly known as exhaustion, which is considered a major cause of failed cancer immunosurveillance. Recent data from models of viral infection show that the precursors of terminally exhausted T cells emerge early during disease course, prior to continuous signalling through the T cell receptor. I speculate that these findings might indicate that, at least in some settings, T cell exhaustion may emerge as a late consequence — rather than an early determinant — of cancer progression. Recent studies in mouse models of viral infection showed that precursors of terminally exhausted T cells emerge early during the course of disease. Here, Galluzzi discusses these findings and what they may mean for our understanding of tumour immunology and responses to immunotherapy with immune checkpoint blockade.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"227-228"},"PeriodicalIF":67.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538303","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":"DOTS: DNA origami tension sensors for studying T cell mechanobiology","authors":"Sarah Al Abdullatif","doi":"10.1038/s41577-025-01152-7","DOIUrl":"10.1038/s41577-025-01152-7","url":null,"abstract":"In this Tools of the Trade article, Sarah Al Abdullatif describes a method to measure — in a physiological context — mechanical forces transmitted between a T cell receptor and its ligand.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"231-231"},"PeriodicalIF":67.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538302","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":"Type 1 immune response reduces seizure risk after traumatic brain injury","authors":"Jennifer S. Y. Ahn, Jennifer L. Gommerman","doi":"10.1038/s41577-025-01154-5","DOIUrl":"10.1038/s41577-025-01154-5","url":null,"abstract":"A preprint by Mroz et al. reports a role for IFNgamma in protecting against seizures after traumatic brain injury.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"234-234"},"PeriodicalIF":67.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532421","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":"Neutrophils release inflammation-resolving vesicles","authors":"Kirsty Minton","doi":"10.1038/s41577-025-01151-8","DOIUrl":"10.1038/s41577-025-01151-8","url":null,"abstract":"Hsu et al. report in Cell that the release of complement-inhibiting vesicles by neutrophils as they age is a self-resolving, anti-inflammatory mechanism that supports a return to homeostasis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"229-229"},"PeriodicalIF":67.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485663","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":"Meningeal Treg cells keep brain in balance","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01148-3","DOIUrl":"10.1038/s41577-025-01148-3","url":null,"abstract":"A study in Science Immunology shows that meningeal regulatory T (Treg) cells limit the activation, proliferation and parenchymal infiltration of T cells and NK cells, indicating that Treg cells act as gatekeepers of the brain.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"156-156"},"PeriodicalIF":67.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417661","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":"Reduced duration of natural protection in the Omicron era","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01145-6","DOIUrl":"10.1038/s41577-025-01145-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"156-156"},"PeriodicalIF":67.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417699","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-mediated strategies to solving the HIV reservoir problem","authors":"Deanna A. Kulpa, Mirko Paiardini, Guido Silvestri","doi":"10.1038/s41577-025-01136-7","DOIUrl":"https://doi.org/10.1038/s41577-025-01136-7","url":null,"abstract":"<p>Antiretroviral therapy (ART) has markedly improved the life-expectancy of people living with HIV. However, during both HIV infection of humans and simian immunodeficiency virus infection of macaques, virus replication almost invariably rebounds upon ART interruption, due to the long-term persistency of a pool of latently infected cells harbouring integrated, replication-competent virus (known as the virus reservoir). Solving this ‘HIV reservoir problem’ is the key to achieving a cure (or at least a persistent remission) for HIV infection. Here, we summarize the key scientific evidence supporting the hypothesis that host immune responses, including those mediated by CD8<sup>+</sup> T cells, B cells, antibodies and innate immune cells, affect the size, clonality, and cellular, tissue and organ distribution of the HIV reservoir. Importantly, we believe that any solution to the ‘reservoir problem’ must address not only the multifaceted interactions between HIV and the host immune system, but also the complex interplay between the immunobiology of memory CD4<sup>+</sup> T helper cells (which form the main virus reservoir) and the molecular mechanisms that regulate HIV latency and reactivation. These concepts provide the rationale to develop new, immune-based approaches to ‘cure’ HIV infection; we review recent efforts to develop such therapies and their efficacy (or lack thereof) in disrupting the establishment and/or persistence of the virus reservoir in preclinical animal models and human clinical trials.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"8 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401370","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":"HDAC9 association with heart disease linked to NLRP3 inflammasome activation","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01144-7","DOIUrl":"10.1038/s41577-025-01144-7","url":null,"abstract":"Loss of a conserved cis-regulatory element at HDAC9 increases NLRP3 inflammasome activation and may explain why HDAC9 is a major risk locus for cardiovascular disease.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"157-157"},"PeriodicalIF":67.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393011","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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