Nature Reviews Immunology最新文献_第9页

Obesity-associated intratumoral acidity promotes pro-tumorigenic macrophages 与肥胖有关的瘤内酸性促进了促肿瘤生成的巨噬细胞

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-28 DOI: 10.1038/s41577-024-01110-9

Kirsty Minton

引用次数: 0

Human macrophages in pancreas and skin shape prenatal organogenesis 胰腺和皮肤中的人类巨噬细胞塑造了产前器官形成过程

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-22 DOI: 10.1038/s41577-024-01106-5

Kirsty Minton

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From TCR fundamental research to innovative chimeric antigen receptor design 从 TCR 基础研究到创新型嵌合抗原受体设计

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41577-024-01093-7

Susana Minguet, Marcela V. Maus, Wolfgang W. Schamel

{"title":"From TCR fundamental research to innovative chimeric antigen receptor design","authors":"Susana Minguet, Marcela V. Maus, Wolfgang W. Schamel","doi":"10.1038/s41577-024-01093-7","DOIUrl":"10.1038/s41577-024-01093-7","url":null,"abstract":"Engineered T cells that express chimeric antigen receptors (CARs) have transformed the treatment of haematological cancers. CARs combine the tumour-antigen-binding function of antibodies with the signalling functions of the T cell receptor (TCR) ζ chain and co-stimulatory receptors. The resulting constructs aim to mimic the TCR-based and co-receptor-based activation of T cells. Although these have been successful for some types of cancer, new CAR formats are needed, to limit side effects and broaden their use to solid cancers. Insights into the mechanisms of TCR signalling, including the identification of signalling motifs that are not present in the TCR ζ chain and mechanistic insights in TCR activation, have enabled the development of CAR formats that outcompete the current CARs in preclinical mouse models and clinical trials. In this Perspective, we explore the mechanistic rationale behind new CAR designs. CAR T cells have transformed the treatment of some haematological cancers. This Perspective explores how insights into T cell receptor signalling have enabled the engineering of CAR formats that can outcompete currently approved CARs in preclinical models and clinical trials.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"212-224"},"PeriodicalIF":67.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452629","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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Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment Vax-Innate：通过调节 T 细胞和肿瘤微环境改进治疗性癌症疫苗

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41577-024-01091-9

Faezzah Baharom, Dalton Hermans, Lélia Delamarre, Robert A. Seder

{"title":"Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment","authors":"Faezzah Baharom, Dalton Hermans, Lélia Delamarre, Robert A. Seder","doi":"10.1038/s41577-024-01091-9","DOIUrl":"10.1038/s41577-024-01091-9","url":null,"abstract":"T cells have a critical role in mediating antitumour immunity. The success of immune checkpoint inhibitors (ICIs) for cancer treatment highlights how enhancing endogenous T cell responses can mediate tumour regression. However, mortality remains high for many cancers, especially in the metastatic setting. Based on advances in the genetic characterization of tumours and identification of tumour-specific antigens, individualized therapeutic cancer vaccines targeting mutated tumour antigens (neoantigens) are being developed to generate tumour-specific T cells for improved therapeutic responses. Early clinical trials using individualized neoantigen vaccines for patients with advanced disease had limited clinical efficacy despite demonstrated induction of T cell responses. Therefore, enhancing T cell activity by improving the magnitude, quality and breadth of T cell responses following vaccination is one current goal for improving outcome against metastatic tumours. Another major consideration is how T cells can be further optimized to function within the tumour microenvironment (TME). In this Perspective, we focus on neoantigen vaccines and propose a new approach, termed Vax-Innate, in which vaccination through intravenous delivery or in combination with tumour-targeting immune modulators may improve antitumour efficacy by simultaneously increasing the magnitude, quality and breadth of T cells while transforming the TME into a largely immunostimulatory environment for T cells. This Perspective considers present and historical paradigms of therapeutic cancer vaccines and describes a conceptual framework, termed Vax-Innate, to simultaneously generate robust tumour-specific T cell responses and remodel the suppressive tumour microenvironment (TME). The authors detail how this strategy could be achieved through systemic vaccination and by using immune modulators to improve dendritic cell and macrophage function in the TME.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"195-211"},"PeriodicalIF":67.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452630","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 roles of arginases and arginine in immunity 精氨酸酶和精氨酸在免疫中的作用

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-17 DOI: 10.1038/s41577-024-01098-2

Stefania Canè, Roger Geiger, Vincenzo Bronte

{"title":"The roles of arginases and arginine in immunity","authors":"Stefania Canè, Roger Geiger, Vincenzo Bronte","doi":"10.1038/s41577-024-01098-2","DOIUrl":"10.1038/s41577-024-01098-2","url":null,"abstract":"Arginase activity and arginine metabolism in immune cells have important consequences for health and disease. Their dysregulation is commonly observed in cancer, autoimmune disorders and infectious diseases. Following the initial description of a role for arginase in the dysfunction of T cells mounting an antitumour response, numerous studies have broadened our understanding of the regulation and expression of arginases and their integration with other metabolic pathways. Here, we highlight the differences in arginase compartmentalization and storage between humans and rodents that should be taken into consideration when assessing the effects of arginase activity. We detail the roles of arginases, arginine and its metabolites in immune cells and their effects in the context of cancer, autoimmunity and infectious disease. Finally, we explore potential therapeutic strategies targeting arginases and arginine. This Review provides an overview of arginine and arginase function in immune cells, at the steady state and during disease. It considers the relevance of this pathway for metabolic, immune and genetic regulation, together with possible therapeutic interventions.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"266-284"},"PeriodicalIF":67.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448108","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 role of the AHR in host–pathogen interactions AHR 在宿主与病原体相互作用中的作用

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-16 DOI: 10.1038/s41577-024-01088-4

Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves

{"title":"The role of the AHR in host–pathogen interactions","authors":"Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves","doi":"10.1038/s41577-024-01088-4","DOIUrl":"10.1038/s41577-024-01088-4","url":null,"abstract":"Host–microorganism encounters take place in many different ways and with different types of outcomes. Three major types of microorganisms need to be distinguished: (1) pathogens that cause harm to the host and must be controlled; (2) environmental microorganisms that can be ignored but must be controlled at higher abundance; and (3) symbiotic microbiota that require support by the host. Recent evidence indicates that the aryl hydrocarbon receptor (AHR) senses and initiates signalling and gene expression in response to a plethora of microorganisms and infectious conditions. It was originally identified as a receptor that binds xenobiotics. However, it was subsequently found to have a critical role in numerous biological processes, including immunity and inflammation and was recently classified as a pattern recognition receptor. Here we review the role of the AHR in host–pathogen interactions, focusing on AHR sensing of different microbial classes, the ligands involved, responses elicited and disease outcomes. Moreover, we explore the therapeutic potential of targeting the AHR in the context of infection. The aryl hydrocarbon receptor (AHR) can sense and initiate immune responses to many different infectious organisms. Here, Moura-Alves and colleagues review the role of the AHR in host–pathogen interactions and explore the therapeutic potential of targeting the AHR in the context of different infectious diseases.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"178-194"},"PeriodicalIF":67.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439691","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

Fever affects T cell fate 发烧会影响 T 细胞的命运

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-11 DOI: 10.1038/s41577-024-01101-w

Lucy Bird

引用次数: 0

Beyond exhaustion: the unique characteristics of CD8+ T cell dysfunction in chronic HBV infection 超越衰竭：慢性 HBV 感染中 CD8+ T 细胞功能障碍的独特特征

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-04 DOI: 10.1038/s41577-024-01097-3

Robert Thimme, Antonio Bertoletti, Matteo Iannacone

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How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia 氧合如何影响免疫反应：生理缺氧和病理缺氧的新作用

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-30 DOI: 10.1038/s41577-024-01087-5

Ananda Shanti Mirchandani, Manuel Alejandro Sanchez-Garcia, Sarah Ruth Walmsley

{"title":"How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia","authors":"Ananda Shanti Mirchandani, Manuel Alejandro Sanchez-Garcia, Sarah Ruth Walmsley","doi":"10.1038/s41577-024-01087-5","DOIUrl":"10.1038/s41577-024-01087-5","url":null,"abstract":"Most eukaryotes require oxygen for their survival and, with increasing multicellular complexity, oxygen availability and delivery rates vary across the tissues of complex organisms. In humans, healthy tissues have markedly different oxygen gradients, ranging from the hypoxic environment of the bone marrow (where our haematopoietic stem cells reside) to the lungs and their alveoli, which are among the most oxygenated areas of the body. Immune cells are therefore required to adapt to varying oxygen availability as they move from the bone marrow to peripheral organs to mediate their effector functions. These changing oxygen gradients are exaggerated during inflammation, where oxygenation is often depleted owing to alterations in tissue perfusion and increased cellular activity. As such, it is important to consider the effects of oxygenation on shaping the immune response during tissue homeostasis and disease conditions. In this Review, we address the relevance of both physiological oxygenation (physioxia) and disease-associated hypoxia (where cellular oxygen demand outstrips supply) for immune cell functions, discussing the relevance of hypoxia for immune responses in the settings of tissue homeostasis, inflammation, infection, cancer and disease immunotherapy. Oxygen levels vary throughout the body and immune cells must adapt to these changes, both during homeostasis and in disease. Here, the authors discuss the impact of physiological subatmospheric oxygen levels (physioxia) as well as disease-related hypoxia on immune cell responses. They consider the therapeutic relevance of understanding how oxygenation affects immune responses in various diseases, including tuberculosis, COVID-19 and cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"161-177"},"PeriodicalIF":67.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329715","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

Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease 将诱导多能干细胞衍生的巨噬细胞作为模拟人类疾病的平台

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-27 DOI: 10.1038/s41577-024-01081-x

Satish Kumar Tiwari, Wei Jie Wong, Marco Moreira, Claudia Pasqualini, Florent Ginhoux

{"title":"Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease","authors":"Satish Kumar Tiwari, Wei Jie Wong, Marco Moreira, Claudia Pasqualini, Florent Ginhoux","doi":"10.1038/s41577-024-01081-x","DOIUrl":"10.1038/s41577-024-01081-x","url":null,"abstract":"Macrophages are innate immune cells that are present in essentially all tissues, where they have vital roles in tissue development, homeostasis and pathogenesis. The importance of macrophages in tissue function is reflected by their association with various human diseases, and studying macrophage functions in both homeostasis and pathological tissue settings is a promising avenue for new targeted therapies that will improve human health. The ability to generate macrophages from induced pluripotent stem (iPS) cells has revolutionized macrophage biology, with the generation of iPS cell-derived macrophages (iMacs) providing unlimited access to genotype-specific cells that can be used to model various human diseases involving macrophage dysregulation. Such disease modelling is achieved by generating iPS cells from patient-derived cells carrying disease-related mutations or by introducing mutations into iPS cells from healthy donors using CRISPR–Cas9 technology. These iMacs that carry disease-related mutations can be used to study the aetiology of the particular disease in vitro. To achieve more physiological relevance, iMacs can be co-cultured in 2D systems with iPS cell-derived cells or in 3D systems with iPS cell-derived organoids. Here, we discuss the studies that have attempted to model various human diseases using iMacs, highlighting how these have advanced our knowledge about the role of macrophages in health and disease. Macrophages are associated with many human diseases but are challenging to study in vivo. Here, Ginhoux and colleagues discuss how iMacs — macrophages generated from induced pluripotent stem (iPS) cells — can enable disease modelling, including through the use of patient-derived iPS cells and 3D organoid co-culture systems. Ultimately, these iMac-based approaches can improve our understanding of macrophage biology in both health and disease.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"108-124"},"PeriodicalIF":67.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328642","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