Cold Spring Harbor perspectives in medicine最新文献_第4页

Corrigendum: Modeling Parkinson's Disease in Primates. 更正：模拟灵长类动物的帕金森病。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-25 DOI: 10.1101/cshperspect.a041802

Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay

引用次数: 0

Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease 检查点抑制剂诱发的自身免疫性糖尿病：一种自身炎症性疾病

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041603

Zoe Quandt, Ana Perdigoto, Mark S. Anderson, Kevan C. Herold

引用次数: 0

Inflammatory β-Cell Stress and Immune Surveillance in Type 1 Diabetes 1 型糖尿病的炎性 β 细胞应激和免疫监视

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041605

Anil Bhushan, Peter J. Thompson

{"title":"Inflammatory β-Cell Stress and Immune Surveillance in Type 1 Diabetes","authors":"Anil Bhushan, Peter J. Thompson","doi":"10.1101/cshperspect.a041605","DOIUrl":"https://doi.org/10.1101/cshperspect.a041605","url":null,"abstract":"Recent years have seen increased recognition for the role of β-cell stress as a contributing factor to the autoimmune destruction process that ultimately results in symptomatic type 1 diabetes (T1D). Preclinical studies have discovered a variety of stress responses in the β-cell that occur at presymptomatic stages and contribute to disease progression, but unifying explanations of how these mechanisms operate to promote disease progression remain incomplete. We propose that stressed β-cells transition into β-cells expressing inflammatory molecules that provoke an immune response to restore homeostasis by coordinating islet repair and the removal of stressed cells. However, when immune surveillance fails, stressed β-cells accumulate and contribute to autoimmunity. Therapies directed toward stressed β-cells to either curb their inflammatory signaling or to eliminate them (essentially doing the job of the failed immune surveillance) are moving from animal models into the clinic with promising initial results, although the understanding of how the immune response is coordinated by stressed β-cells is not clear. In this article, we discuss β-cell stress responses implicated in T1D pathogenesis based on evidence from humans and highlight existing knowledge gaps in their mechanisms. Future work in this field is poised to target T1D by simultaneously targeting stressed β-cells and the failed immune response to halt the progression of autoimmunity and prevent β-cell destruction.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"45 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Cross Talk between β Cells and Immune Cells: What We Know, What We Think We Know, and What We Should Learn β细胞与免疫细胞之间的交叉对话：我们知道什么、我们认为我们知道什么以及我们应该了解什么

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041604

Fatoumata Samassa, Capucine Holtzmann, Roberto Mallone

{"title":"Cross Talk between β Cells and Immune Cells: What We Know, What We Think We Know, and What We Should Learn","authors":"Fatoumata Samassa, Capucine Holtzmann, Roberto Mallone","doi":"10.1101/cshperspect.a041604","DOIUrl":"https://doi.org/10.1101/cshperspect.a041604","url":null,"abstract":"Type 1 diabetes (T1D) is a disease whose pathogenesis is driven by both immune dysregulation and β-cell dysfunction. While the specialized structure and function of β cells make them vulnerable to autoimmunity, several surface receptor/ligand pairs underlie the cross talk engaged with T lymphocytes and other immune subsets. The expression of these ligands on β cells is coordinately up-regulated by the exposure to interferons, notably the type I interferons that represent the signature cytokines since the early preclinical stages of T1D. Yet, their interaction with receptors expressed on T lymphocytes can favor either β-cell vulnerability or protection. Despite several knowledge gaps, this novel holistic view of autoimmunity that incorporates both immune and β-cell-derived pathogenic drivers is starting to translate into novel therapeutic strategies aimed at decreasing vulnerability and/or increasing these protective mechanisms. This review summarizes the current knowledge in this evolving field, the assumptions that are often taken for granted but lack formal evidence, and the blind spots in this landscape that may hide further therapeutic opportunities.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"20 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Immunotherapies for Childhood Cancer. 儿童癌症免疫疗法。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041574

Jeong A Park, Nai-Kong V Cheung

{"title":"Immunotherapies for Childhood Cancer.","authors":"Jeong A Park, Nai-Kong V Cheung","doi":"10.1101/cshperspect.a041574","DOIUrl":"10.1101/cshperspect.a041574","url":null,"abstract":"Children are surviving cancer in greater numbers than ever. Over the last 50 years, substantial advancements in pediatric cancer treatment have resulted in an 85% 5-year survival rate. Nonetheless, a notable 10%-15% of patients encounter relapse or develop refractory disease, leading to significantly lower survival. Recent attempts to further intensify cytotoxic chemotherapy have failed due to either severe toxicities or ineffectiveness, highlighting the need for new treatment strategies. Immunotherapies are emerging and expanding their clinical application to a wide array of cancers, including those affecting children. In pediatric cancers, monoclonal antibodies targeting GD2 have demonstrated durable radiographic and histologic responses in neuroblastoma (NB), and CD19-targeted bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T cells have likewise changed the outlook for refractory acute lymphoblastic leukemia (ALL) in children. This review discusses the clinical development of immunotherapies for pediatric cancers, focusing on pediatric ALL and NB, two major pediatric cancers transformed by immunotherapy, updates on the recent advancements in immunotherapies, and further discusses the future directions of immunotherapy for pediatric cancers.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Metabolic Reprogramming in Human Cancer Patients and Patient-Derived Models. 人类癌症患者和患者衍生模型的代谢重编程。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041552

Teresa W-M Fan, Richard M Higashi, Andrew N Lane

{"title":"Metabolic Reprogramming in Human Cancer Patients and Patient-Derived Models.","authors":"Teresa W-M Fan, Richard M Higashi, Andrew N Lane","doi":"10.1101/cshperspect.a041552","DOIUrl":"https://doi.org/10.1101/cshperspect.a041552","url":null,"abstract":"Stable isotope-resolved metabolomics delineates reprogrammed intersecting metabolic networks in human cancers. Knowledge gained from in vivo patient studies provides the \"benchmark\" for cancer models to recapitulate. It is particularly difficult to model patients' tumor microenvironment (TME) with its complex cell-cell/cell-matrix interactions, which shapes metabolic reprogramming crucial to cancer development/drug resistance. Patient-derived organotypic tissue cultures (PD-OTCs) represent a unique model that retains an individual patient's TME. PD-OTCs of non-small-cell lung cancer better recapitulated the in vivo metabolic reprogramming of patient tumors than the patient-derived tumor xenograft (PDTX), while enabling interrogation of immunometabolic response to modulators and TME-dependent resistance development. Patient-derived organoids (PDOs) are also good models for reconstituting TME-dependent metabolic reprogramming and for evaluating therapeutic responses. Single-cell based 'omics on combinations of PD-OTC and PDO models will afford an unprecedented understanding on TME dependence of human cancer metabolic reprogramming, which should translate into the identification of novel metabolic targets for regulating TME interactions and drug resistance.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Hyperactive Ras Signaling in Pediatric Cancer. 靶向小儿癌症中亢进的 Ras 信号

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041572

Anya Levinson, Kevin Shannon, Benjamin J Huang

引用次数: 0

Modeling Parkinson's Disease in Primates. 灵长类动物的帕金森病模型

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041612

Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay

引用次数: 0

Principles in the Development of Contemporary Treatment of Childhood Malignancies: The First 75 Years. 当代儿童恶性肿瘤治疗发展的原则：前 75 年。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041634

Katie A Greenzang, Stephen E Sallan

{"title":"Principles in the Development of Contemporary Treatment of Childhood Malignancies: The First 75 Years.","authors":"Katie A Greenzang, Stephen E Sallan","doi":"10.1101/cshperspect.a041634","DOIUrl":"https://doi.org/10.1101/cshperspect.a041634","url":null,"abstract":"Over the last 75 years, pediatric cancer has gone from nearly universally fatal, to having a >80% chance of long-term survival. Below we share highlights in this 75-year history, beginning with the \"birth\" of chemotherapy in treating childhood leukemia, through the development of multiagent chemotherapy, risk-stratified therapy, the use of molecular strategies in diagnosis and treatment, and adapting treatment to the needs of particularly vulnerable patient groups such as adolescents and young adults (AYAs). While pediatric leukemia treatment demonstrates the ever-improving cures achieved through iterative incorporation of novel discoveries, this experience is contrasted with that of osteosarcoma, where scientific advances made over recent decades have yet to be translated into meaningful improvements in long-term survival. We conclude with a brief overview of current areas of focus, including precision medicine, immunotherapy, and other treatment advancements, yet describe the need to couple these scientific breakthroughs with consideration of equitable access and evaluation of the long-term impacts of these \"newer\" therapies in survivorship. Substantial further work is needed to achieve our goal of curing all children with cancer as harmlessly as possible.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Imaging Tumor Metabolism. 肿瘤代谢成像。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI: 10.1101/cshperspect.a041551

Thomas Ruan, Kayvan R Keshari

引用次数: 0