Nature Reviews Immunology最新文献

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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
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
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
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
Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape. 黑色素瘤新辅助免疫治疗的经验教训:了解抗肿瘤免疫和肿瘤逃逸。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-09-22 DOI: 10.1038/s41577-025-01222-w
Francesca Fallarino,Christian U Blank
{"title":"Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.","authors":"Francesca Fallarino,Christian U Blank","doi":"10.1038/s41577-025-01222-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01222-w","url":null,"abstract":"Immunotherapy has become a fourth pillar of cancer therapy, alongside surgery, radiotherapy and chemotherapy. Cancer immunotherapy seems to be most effective in the context of low but not negligible tumour burden, thus in the neoadjuvant setting before curative intent surgery. Indeed, in the case of macroscopic stage III melanoma, a decade of clinical and translational research has led to conclusive evidence that neoadjuvant immunotherapy should be the clinical standard of care, although its adoption in different regions of the world is still ongoing. In this Perspective, we discuss the lessons learnt from neoadjuvant immunotherapy trials in melanoma and where the field is heading next. In the coming years, we believe that biomarker-driven personalization of the therapy, a deeper understanding of the role of immune education, and the ability to uncouple toxicity from efficacy will make neoadjuvant cancer immunotherapy safer and more effective, not only for melanoma but also for other types of cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"11 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117050","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
Clearing the hurdles for CAR-T cell treatment. 清除CAR-T细胞治疗的障碍。
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-09-22 DOI: 10.1038/s41577-025-01228-4
Rayne H Rouce
{"title":"Clearing the hurdles for CAR-T cell treatment.","authors":"Rayne H Rouce","doi":"10.1038/s41577-025-01228-4","DOIUrl":"https://doi.org/10.1038/s41577-025-01228-4","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"61 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117051","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
Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation 免疫相关放线菌病处于免疫缺陷、自身免疫和自身炎症的交叉路口
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-09-10 DOI: 10.1038/s41577-025-01214-w
Loïc Dupré, Irinka Castanon, Kaan Boztug
{"title":"Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation","authors":"Loïc Dupré, Irinka Castanon, Kaan Boztug","doi":"10.1038/s41577-025-01214-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01214-w","url":null,"abstract":"<p>Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell–cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is highlighted by the discovery of inborn errors of immunity (IEIs) that are caused by defects in individual actin-regulatory proteins, resulting in immune-related actinopathies. In addition to susceptibility to infection, these often present with a vast array of autoimmune and autoinflammatory manifestations. Here, we review the role of actin subnetworks in the activation and function of lymphoid and myeloid cells. We focus on the mechanisms by which actin defects result in aberrant lymphocyte function, including dysregulation of T cell- and B cell-mediated tolerance and biased cytokine production, which can result in autoimmunity. We also highlight the relationship between actin defects and inflammasome activation and other pathomechanisms in myeloid cells as the underlying cause of autoinflammation. Finally, we discuss future avenues for research and therapeutic intervention based on a molecular understanding of immune-related actinopathies.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"14 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031961","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
B cell trailblazers connect EBV to MS B细胞开拓者将EBV与MS联系起来
IF 60.9 1区 医学
Nature Reviews Immunology Pub Date : 2025-09-01 DOI: 10.1038/s41577-025-01224-8
Lucy Bird
{"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}
引用次数: 0
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