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Annual Review of Pathology-Mechanisms of Disease最新文献

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Mechanisms of Norovirus Immunity: Implications for Vaccine Design. 诺如病毒免疫机制：对疫苗设计的启示。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-042524-021922
Arya B Ökten,Joseph E Craft,Craig B Wilen
{"title":"Mechanisms of Norovirus Immunity: Implications for Vaccine Design.","authors":"Arya B Ökten,Joseph E Craft,Craig B Wilen","doi":"10.1146/annurev-pathmechdis-042524-021922","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-021922","url":null,"abstract":"Human noroviruses are the predominant cause of acute gastroenteritis globally, causing significant morbidity and mortality especially in low- and middle-income countries. Despite this immense public health burden, there are no commercially available vaccines or antiviral drugs, highlighting a critical unmet medical need. Norovirus vaccine development faces several challenges including extensive viral diversity and limited mechanistic understanding of protective immunity. While several vaccine candidates-including virus-like particle, adenovirus-vector, and mRNA-lipid nanoparticle vaccines-are in clinical trials, none have achieved complete protection in adults or demonstrated efficacy in young children. Understanding the mechanisms underlying norovirus immunity and the relative importance of mucosal responses remains crucial for vaccine optimization. Continued research addressing these basic questions, along with strategic antigen selection and platform optimization, are essential to overcome current limitations to the development of broadly protective norovirus vaccines.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"356 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305628","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
Genomic Taxonomy of Aggressive B-Cell Lymphoid Neoplasms. 侵袭性b细胞淋巴样肿瘤的基因组分类学。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-111523-023413
Laura K Hilton,Brett Collinge,David W Scott
{"title":"Genomic Taxonomy of Aggressive B-Cell Lymphoid Neoplasms.","authors":"Laura K Hilton,Brett Collinge,David W Scott","doi":"10.1146/annurev-pathmechdis-111523-023413","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023413","url":null,"abstract":"Aggressive B-cell lymphomas are a heterogeneous group of neoplasms, organized in the current classifications into more than 20 categories on the basis of morphology, immunophenotype, clinical presentation, and limited molecular features. Over the past 25 years, there has been an exponential accumulation of detailed genomic characterizations of these lymphomas. Many defined categories have been confirmed as relatively homogeneous, fulfilling the classification ideal of sharing core biological hallmarks. However, the largest group, diffuse large B-cell lymphoma, not otherwise specified, which makes up 70-74% of the patients, has been revealed to be remarkably heterogeneous at a genomic and biological level. In this review, we summarize the current state of knowledge and then propose an evolution of the classification of aggressive B-cell lymphomas to a genomics-informed taxonomy based around normal B-cell development and the different modes by which lymphomas achieve key hallmarks of cancer-hallmarks that can inform on patient management.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"104 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305333","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
Molecular Mechanisms of Respiratory Syncytial Virus Pathogenesis. 呼吸道合胞病毒发病机制的分子机制。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-042424-114052
Madison J Granoski,Aleksandra Stojic,Stephen Z Lee,David J Marchant
{"title":"Molecular Mechanisms of Respiratory Syncytial Virus Pathogenesis.","authors":"Madison J Granoski,Aleksandra Stojic,Stephen Z Lee,David J Marchant","doi":"10.1146/annurev-pathmechdis-042424-114052","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042424-114052","url":null,"abstract":"Respiratory syncytial virus (RSV) is one of the leading causes of infant hospitalization and mortality worldwide. RSV pathogenesis is a result of various virus-host interactions. While significant work has been done to elucidate mechanisms of RSV pathogenesis at a systemic level from the host perspective, here we examine how RSV pathogenesis occurs on a molecular level. While each RSV protein plays an essential role in establishing and advancing disease, each one also executes multifaceted strategies for evasion of host detection. In this review, we outline how each component of the RSV replication cycle works to co-opt host cell proteins and modulate host immune responses during entry, transcription, replication, translation, assembly, and egress. We examine the latest literature regarding RSV protein function and discuss outstanding questions in the field.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"33 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305334","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
Molecular Pathogenesis of Uterine Sarcomas: Mechanisms and Implications for Treatment. 子宫肉瘤的分子发病机制及其治疗意义。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-14 DOI: 10.1146/annurev-pathmechdis-111523-023434
Sarah Chiang
{"title":"Molecular Pathogenesis of Uterine Sarcomas: Mechanisms and Implications for Treatment.","authors":"Sarah Chiang","doi":"10.1146/annurev-pathmechdis-111523-023434","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023434","url":null,"abstract":"Uterine sarcomas are rare cancers with diverse clinical, histologic, and genomic profiles. At the genetic level, they can be classified into simple and complex genomic sarcomas, exemplified by endometrial stromal sarcoma (ESS) and uterine leiomyosarcoma (uLMS), respectively. Sequencing technologies in research and clinical settings have significantly advanced the molecular understanding of these tumors. New entities characterized by distinctive morphologies and genomic alterations have expanded the category of uterine sarcomas with simple genomes beyond ESS to include variant uLMS and fibrosarcoma-like uterine sarcoma (FUS). Molecular profiling of uLMS has also uncovered possible therapeutic targets in the most common type of uterine sarcoma, where prognostication and clinical management remain challenging. This review discusses the current histologic and molecular classification of low- and high-grade ESS, FUS, and conventional and variant uLMS and explores the potential impact of the genetic alterations observed in these uterine sarcomas on treatment.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"13 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288204","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 Genome Stability to Mitigate Human Aging and Disease. 靶向基因组稳定性减缓人类衰老和疾病。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-14 DOI: 10.1146/annurev-pathmechdis-042624-105942
Debra Toiber,Björn Schumacher
{"title":"Targeting Genome Stability to Mitigate Human Aging and Disease.","authors":"Debra Toiber,Björn Schumacher","doi":"10.1146/annurev-pathmechdis-042624-105942","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042624-105942","url":null,"abstract":"The maintenance of a stable genome requires constant repair. Congenital DNA repair defects lead to cancer susceptibility and progeroid (premature aging-like) syndromes. Even with intact repair, DNA lesions accumulate in aging organisms, leading to replication and transcription stress and age-dependent somatic mutations. These, in turn, can compromise cellular function and elevate cancer risk. DNA damage response (DDR) mechanisms can lead to cellular death and senescence, and targeting the DDR has emerged as therapeutic strategy not only in cancer but also to protect from age-associated phenotypes. Inhibiting DNA repair can promote cancer cell death. Eliminating senescent cells may alleviate proinflammatory consequences on their tissue environment. Moreover, strategies to limit DNA damage and augment repair in normal cells are in active development. Here, we review emerging concepts for targeting genome maintenance mechanisms to lower cancer risk and lengthen healthy lifespan by extending the integrity and functionality of somatic genomes.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"8 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288203","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
Zonation, Zonation, Zonation: The Real Estate of the Liver 分区，分区，分区：肝脏的房地产
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-13 DOI: 10.1146/annurev-pathmechdis-042624-091820
Tyler M. Yasaka, Chang Kyung Kim, Vik Meadows, Satdarshan P. Monga
{"title":"Zonation, Zonation, Zonation: The Real Estate of the Liver","authors":"Tyler M. Yasaka, Chang Kyung Kim, Vik Meadows, Satdarshan P. Monga","doi":"10.1146/annurev-pathmechdis-042624-091820","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042624-091820","url":null,"abstract":"The liver serves as a central hub for a diverse set of functions including metabolic homeostasis, detoxification, and protein synthesis. While appearing homogeneous, hepatocytes, the major workhorse in the liver, demonstrate spatial identity within the lobule, which in turn dictates gene and protein expression and, eventually, function. Presenting as an axis from the portal triad to the central vein, this organization has been conventionally referred to as metabolic zonation. In recent years, the heterogeneity in expression and function is now understood to extend well beyond hepatocytes and metabolism to include nonparenchymal cells and diverse functions. Although the lobule is conventionally divided into three zones, spatial multi-omics technologies reveal a more nuanced picture, where zonation provides a coordinate system for an eclectic but highly functional hepatic milieu. We summarize the current understanding of liver zonation as it contributes to division of labor, injury compartmentalization, and stepwise arrangement of metabolic pathways and discuss the implications of this framework for liver homeostasis, regeneration, and disease.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"7 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282668","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
Gasdermins, Executors of Pyroptosis: A Decade in Perspective. Gasdermins，焦亡的执行者：十年的观点。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-09 DOI: 10.1146/annurev-pathmechdis-042624-121548
Bowen Zhou,Derek Abbott
{"title":"Gasdermins, Executors of Pyroptosis: A Decade in Perspective.","authors":"Bowen Zhou,Derek Abbott","doi":"10.1146/annurev-pathmechdis-042624-121548","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042624-121548","url":null,"abstract":"Pyroptosis is a molecularly defined pathway of cell death and lysis relying on formation of membrane pores by the family of gasdermin proteins. Since the characterization of prototypical gasdermin D in 2015, intense effort in the past decade has shed light on protease-dependent activation of these agents of cellular demise in human health and disease, although cell death-independent functions do exist. Numerous regulatory mechanisms ranging from posttranslational modification, control of expression, and overlap in activation systems have been described, but pharmacologic control of gasdermins is still in its infancy. Thus, gasdermin-specific targeting in disease has not yet been achieved outside of a few select cases. This review summarizes these findings broadly from a perspective of biological mechanisms and highlights the forthcoming challenges hindering bench-to-bedside adoption of this knowledge.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"39 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254532","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
Immunopathology of Glioblastoma 胶质母细胞瘤的免疫病理学
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-08 DOI: 10.1146/annurev-pathmechdis-042524-025950
Jiabo Li, James L. Ross, Dolores Hambardzumyan, Daniel J. Brat
{"title":"Immunopathology of Glioblastoma","authors":"Jiabo Li, James L. Ross, Dolores Hambardzumyan, Daniel J. Brat","doi":"10.1146/annurev-pathmechdis-042524-025950","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-025950","url":null,"abstract":"Glioblastoma (GBM), the most frequent and malignant primary brain tumor, is characterized by a highly diverse and profoundly immunosuppressive tumor microenvironment (TME) that provides an unconstrained environment for tumor progression and significantly complicates therapeutic interventions. Despite advances in immunotherapeutic approaches, such as chimeric antigen receptor T cell and immune checkpoint inhibitors, efficacy remains limited due to the complexity of the GBM TME and robust immune evasion mechanisms. In this review, we elucidate the intricate interplay among cellular components within the TME that lead to this immunosuppressive state, including tumor-associated macrophages/microglia, myeloid-derived suppressor cells, regulatory T cells, and glioma stem cells, as well as other critical elements that contribute to TME complexity, such as the severe hypoxia associated with central necrosis, the blood–brain barrier, and the extracellular matrix. This review also highlights mechanisms of immune evasion and recent immunotherapeutic approaches along with their biologic rationale, underscoring the need for integrated therapeutic strategies that both target immunosuppressive elements and enhance immune activation.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"36 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246942","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
Molecular Subtypes of Neuroendocrine Carcinoma: From Chaos to Consensus. 神经内分泌癌的分子亚型：从混乱到一致。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-08 DOI: 10.1146/annurev-pathmechdis-042524-023153
Zhanyu Wang,Nan Sun,Jie He,Esther Redin,Charles M Rudin
{"title":"Molecular Subtypes of Neuroendocrine Carcinoma: From Chaos to Consensus.","authors":"Zhanyu Wang,Nan Sun,Jie He,Esther Redin,Charles M Rudin","doi":"10.1146/annurev-pathmechdis-042524-023153","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-023153","url":null,"abstract":"Neuroendocrine carcinomas (NECs) represent a notoriously aggressive family of lethal malignancies arising across diverse anatomical sites. Molecular subtyping based on key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 has significantly advanced understanding of tumor heterogeneity in small cell lung cancer (SCLC). Beyond SCLC, extrapulmonary NECs demonstrate analogous heterogeneity, similarly governed by these transcriptional determinants. Recent studies have further identified a fifth subtype driven by the lineage-specifying factor HNF4A. This review aims to propose a unified pan-NEC classification framework for consistent molecular subtyping across pulmonary, gastro-entero-pancreatic (GEP), and genitourinary systems. We delineate the distinct lineage hallmarks of the ANHPY subtypes (neuroendocrine, neuronal, GEP-like, tuft-like, and epithelial-mesenchymal transition phenotypes) and explore their connections to defining mechanisms, genetic alterations, clinicopathological features, and therapeutic vulnerabilities. This unified framework serves as a molecular roadmap for precise NEC research and management.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"62 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246559","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
Role of Chromatin Looping Factors in Leukemia. 染色质环化因子在白血病中的作用。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-09-15 DOI: 10.1146/annurev-pathmechdis-051222-014420
Shira G Glushakow-Smith,Zuzana Tothova
{"title":"Role of Chromatin Looping Factors in Leukemia.","authors":"Shira G Glushakow-Smith,Zuzana Tothova","doi":"10.1146/annurev-pathmechdis-051222-014420","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-051222-014420","url":null,"abstract":"Genomic organization requires an intricate balance between the compact storage of genetic material and the ability to finely tune gene regulation. Chromatin looping achieves this balance by organizing concordantly regulated groups of genes and their regulatory elements into loops while also condensing DNA to fit into the small volume of a nucleus. A number of DNA-binding and associated proteins, including CTCF and cohesin, act as chromatin looping factors that mediate this process. Given the tight association between chromatin looping and gene expression, disordered genomic organization has been linked to disease development, including cancer. Recurrent mutations in chromatin looping factors are common in cancer, in particular blood cancers such as leukemia and myelodysplastic syndromes. In this review, we describe the evolution of our understanding of the chromatin looping process in healthy and malignant hematopoiesis and discuss the therapeutic potential of targeting chromatin looping factors in leukemia.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"72 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068435","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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