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Astroimmunology: the effects of spaceflight and its associated stressors on the immune system. 太空免疫学：太空飞行及其相关压力源对免疫系统的影响。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-16 DOI: 10.1038/s41577-025-01226-6
Daniel A Winer,Huixun Du,JangKeun Kim,Veronica Chang,Marissa Burke,Shawn Winer,Sylvain V Costes,Jean-Pol Frippiat,Clarence Sams,Amber M Paul,Honglu Wu,Oliver Ullrich,Sarah Baatout,Afshin Beheshti,Christopher E Mason,Alexander Choukér,Brian E Crucian
{"title":"Astroimmunology: the effects of spaceflight and its associated stressors on the immune system.","authors":"Daniel A Winer,Huixun Du,JangKeun Kim,Veronica Chang,Marissa Burke,Shawn Winer,Sylvain V Costes,Jean-Pol Frippiat,Clarence Sams,Amber M Paul,Honglu Wu,Oliver Ullrich,Sarah Baatout,Afshin Beheshti,Christopher E Mason,Alexander Choukér,Brian E Crucian","doi":"10.1038/s41577-025-01226-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01226-6","url":null,"abstract":"As humans embark on longer and deeper missions into space, it is crucial to understand how spaceflight impacts the immune system. Decades of discoveries, bolstered by recent multiomic analyses, have identified key immune processes that are affected by the spaceflight environment. These findings form the foundations of the emerging field of 'astroimmunology'. Spaceflight stressors - such as microgravity and galactic cosmic radiation - and other mission-associated variables, including psychological stress and abnormal circadian rhythms, can disrupt or adversely affect immune cell biology. In addition, spaceflight alters host-microbiome interactions, which can increase susceptibility to opportunistic pathogens and viral reactivation. Although ground-based analogues for human spaceflight have provided insights into these stressors individually, their combined effects during spaceflight remain less understood. This Review explores our current knowledge of the effects of spaceflight stressors on the immune system and the clinical implications for human space exploration. It also highlights current and developing countermeasures, including machine-learning approaches, advanced monitoring technologies and standardized biobanking, that can facilitate research into the impact of spaceflight on the immune system. Looking ahead, progressing from low Earth orbit missions to long-term missions to the Moon, Mars and beyond will introduce new challenges, including increased radiation, variable gravity and regolith exposure. We discuss these prospective challenges and outline potential preventive and mitigative strategies for sustaining immune health to enable safe and effective space exploration and habitation of distant worlds.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"13 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305720","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
Microenvironmental regulation of solid tumour resistance to CAR T cell therapy. 实体肿瘤对CAR - T细胞疗法耐药的微环境调控。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-14 DOI: 10.1038/s41577-025-01229-3
Zachary L Lamplugh,Nils Wellhausen,Carl H June,Yi Fan
{"title":"Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.","authors":"Zachary L Lamplugh,Nils Wellhausen,Carl H June,Yi Fan","doi":"10.1038/s41577-025-01229-3","DOIUrl":"https://doi.org/10.1038/s41577-025-01229-3","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy holds significant promise for the treatment of cancer; however, its efficacy in solid tumours is substantially hindered by the immunosuppressive tumour microenvironment (TME). Solid tumours can resist immunotherapy by impairing T cell trafficking, function and persistence. One of the initial obstacles that CAR T cells encounter is the abnormal tumour vasculature, which restricts efficient T cell infiltration, further compounded by a dense extracellular matrix. CAR T cells that do infiltrate the tumours are outnumbered by immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages. Additionally, tumour cells can contribute to CAR T cell resistance by upregulating immune checkpoint molecules, such as PDL1 and CTLA4, and engage in metabolic competition. In this Review, we discuss how cellular and non-cellular components of the TME impair CAR T cell therapy and consider potential strategies to improve CAR T cell therapies for solid tumours, either by reprogramming the TME or by engineering CAR T cells to resist the immunosuppressive effects of the TME.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"54 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288399","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
Targeting organelle function in T cells for cancer immunotherapy. 靶向T细胞细胞器功能用于癌症免疫治疗。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-09 DOI: 10.1038/s41577-025-01223-9
Jeremy G Baldwin,Christoph Heuser-Loy,Luca Gattinoni
{"title":"Targeting organelle function in T cells for cancer immunotherapy.","authors":"Jeremy G Baldwin,Christoph Heuser-Loy,Luca Gattinoni","doi":"10.1038/s41577-025-01223-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01223-9","url":null,"abstract":"Organelles are the internal batteries, gears, actuators, 3D printers and transmitters that drive cell function. Their composition and activity vary between cell types depending on functional demands. In T cells, which are key mediators of immunosurveillance and tumour eradication, organelles are relatively few and function at basal levels when cells are at rest. However, upon activation, they increase in number and size and undergo extensive remodelling to support rapid proliferation, effector differentiation and adaptation to diverse microenvironments, including the tumour microenvironment, thereby enabling efficient clearance of target cells. In this Review, we provide an overview of recent advances in our understanding of how various organelles contribute to T cell-mediated antitumour immunity. We also discuss emerging strategies to modulate organelle functions - from organelle-targeted therapies and their use as cargo delivery systems to the transfer or transplantation of native or synthetic organelles - that have the potential to enhance cancer immunotherapies involving immune-checkpoint blockade or the adoptive transfer of T cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"18 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254762","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
Autoimmune T cells identified in ALS. 在ALS中发现的自身免疫T细胞。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-08 DOI: 10.1038/s41577-025-01233-7
Yvonne Bordon
{"title":"Autoimmune T cells identified in ALS.","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01233-7","DOIUrl":"https://doi.org/10.1038/s41577-025-01233-7","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"10 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246599","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
Enterobacteriaceae-derived cadaverine manipulates gut macrophage metabolism. 肠杆菌科衍生的尸胺操纵肠道巨噬细胞代谢。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-07 DOI: 10.1038/s41577-025-01234-6
Alexandra Flemming
{"title":"Enterobacteriaceae-derived cadaverine manipulates gut macrophage metabolism.","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01234-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01234-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"58 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241099","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
ILC2-neuron cross-talk regulates pain sensitivity and gait. ilc2神经元串扰调节疼痛敏感性和步态。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-07 DOI: 10.1038/s41577-025-01235-5
Alexandra Flemming
{"title":"ILC2-neuron cross-talk regulates pain sensitivity and gait.","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01235-5","DOIUrl":"https://doi.org/10.1038/s41577-025-01235-5","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"18 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240874","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
Proteotoxic shock is a mechanistic driver of T cell exhaustion. 蛋白毒性休克是T细胞耗竭的机制驱动因素。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-07 DOI: 10.1038/s41577-025-01236-4
Alexandra Flemming
{"title":"Proteotoxic shock is a mechanistic driver of T cell exhaustion.","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01236-4","DOIUrl":"https://doi.org/10.1038/s41577-025-01236-4","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"128 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241098","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 promise of immunotherapy for central nervous system tumours. 免疫疗法治疗中枢神经系统肿瘤的前景。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-06 DOI: 10.1038/s41577-025-01227-5
Jasia Mahdi,Vrunda Trivedi,Michelle Monje
{"title":"The promise of immunotherapy for central nervous system tumours.","authors":"Jasia Mahdi,Vrunda Trivedi,Michelle Monje","doi":"10.1038/s41577-025-01227-5","DOIUrl":"https://doi.org/10.1038/s41577-025-01227-5","url":null,"abstract":"The nervous and immune systems are intricately linked to one another through bi-directional crosstalk. Given the limited therapeutic options for aggressive and refractory central nervous system (CNS) tumours, immunotherapies are increasingly being explored as potential treatments for these malignancies. In this Review, we provide an overview of the nervous system-immune system connections that provide the basis for the use of immunotherapy to treat CNS tumours. We then summarize the outcomes from preclinical and clinical studies that have used immunotherapies, including chimeric antigen receptor T cell therapy, oncolytic viruses, cancer vaccines and immune-checkpoint inhibitors, for the treatment of primary CNS cancers such as high-grade gliomas, refractory embryonal brain tumours and primary CNS lymphomas. Finally, we review the neurological symptoms and syndromes that can arise with these immunotherapeutic approaches.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"10 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235978","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
Skin Treg cells set the tone for neuronal activation. 皮肤Treg细胞为神经元的激活定下基调。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-03 DOI: 10.1038/s41577-025-01232-8
Kirsty Minton
{"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}
引用次数: 0
Regulators of CD8+ T cell exhaustion. CD8+ T细胞耗竭的调节因子。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-10-01 DOI: 10.1038/s41577-025-01221-x
Qinli Sun,Chen Dong
{"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}
引用次数: 0
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