Cell Reports Medicine最新文献_第7页

Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma. 原发性和复发性套细胞淋巴瘤的肿瘤进化和免疫微环境动力学。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-27 DOI: 10.1016/j.xcrm.2025.102318

Hui Wan, Weicheng Ren, Mingyu Yang, Man Nie, Agata M Wasik, Likun Du, Leire de Campos-Mata, Rui Sun, Zhiliang Bai, Archibald Enninful, Yating Wang, Mattias Berglund, Rose-Marie Amini, Xiaobo Li, Chunli Yang, Xiaofei Ye, Zhi-Zhang Yang, Stephen M Ansell, Dongbing Liu, Mirjam van der Burg, Rong Fan, Kui Wu, Birgitta Sander, Qiang Pan-Hammarström

{"title":"Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma.","authors":"Hui Wan, Weicheng Ren, Mingyu Yang, Man Nie, Agata M Wasik, Likun Du, Leire de Campos-Mata, Rui Sun, Zhiliang Bai, Archibald Enninful, Yating Wang, Mattias Berglund, Rose-Marie Amini, Xiaobo Li, Chunli Yang, Xiaofei Ye, Zhi-Zhang Yang, Stephen M Ansell, Dongbing Liu, Mirjam van der Burg, Rong Fan, Kui Wu, Birgitta Sander, Qiang Pan-Hammarström","doi":"10.1016/j.xcrm.2025.102318","DOIUrl":"10.1016/j.xcrm.2025.102318","url":null,"abstract":"Mantle cell lymphoma (MCL) is a rare but often aggressive type of B cell lymphoma with a high risk of relapse. To explore intratumoral clonal diversity and tumor evolution related to disease relapse, we integrate single-cell RNA and B cell receptor sequencing with whole-genome sequencing in 20 diagnosed/untreated and/or relapsed samples from 11 MCL patients. Our results reveal significant intratumor heterogeneity in MCL already at diagnosis. We further show that the evolutionary paths during disease progression for each patient are unique, where minor clones present at diagnosis may acquire different mutations and copy-number variations and/or migrate to various microenvironments. Despite significant interpatient heterogeneity, recurrent genetic and transcriptomic changes in tumor cells affecting key signaling pathways, along with alterations involved in the tumor microenvironment, are also observed during disease progression. Taken together, our findings elucidate the diverse and dynamic tumor-immune evolution processes associated with disease progression and relapse in MCL.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102318"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo neutrophils hitchhiking for tumor targeting and microenvironment regulation boosts oncolytic virus therapy. 体内中性粒细胞搭便车肿瘤靶向和微环境调节促进溶瘤病毒治疗。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-25 DOI: 10.1016/j.xcrm.2025.102314

Xu Zhao, Hanwei Huang, Mingyang Liu, Pengliang Wang, Shuhui Song, Zhenguo Cheng, Yang Yu, Fengming Liu, Yaohe Wang, Zhiqing Pang, Hongjun Li, Funan Liu

{"title":"In vivo neutrophils hitchhiking for tumor targeting and microenvironment regulation boosts oncolytic virus therapy.","authors":"Xu Zhao, Hanwei Huang, Mingyang Liu, Pengliang Wang, Shuhui Song, Zhenguo Cheng, Yang Yu, Fengming Liu, Yaohe Wang, Zhiqing Pang, Hongjun Li, Funan Liu","doi":"10.1016/j.xcrm.2025.102314","DOIUrl":"10.1016/j.xcrm.2025.102314","url":null,"abstract":"Neutrophils constitute a substantial proportion of the immune cell population infiltrating tumors, where they play a pivotal role in establishing an immunosuppressive microenvironment to facilitate tumor growth. Our clinical investigation has unveiled that, following oncolytic virus (OV) treatment, immunosuppressive neutrophils could lead to T cell exhaustion and compromised antitumor efficacy. In this study, we devise a dual-functional conjugation strategy that enables OVs to selectively bind with circulating neutrophils and initiate their death. Prior to dysfunction, neutrophils can harbor OVs and facilitate their infiltration into tumors, leading to a 5.38-fold increase in OV levels within tumors compared to direct intravenous injection. Additionally, infiltrated neutrophils undergo dying after 8 h, which promotes T cell priming, reduces T cell exhaustion, and remodels the tumor immune microenvironment. Our findings illuminate the determinants influencing the efficacy of OVs and propose targeted solutions, thereby offering insights for the clinical translation of these therapeutic agents.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102314"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Large language models enable tumor-type classification and localization of cancers of unknown primary from genomic data. 大型语言模型能够从基因组数据中对未知原发癌症进行肿瘤类型分类和定位。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-09-04 DOI: 10.1016/j.xcrm.2025.102332

Jilei Liu, Meng Yang, Yajing Bi, Junqing Zhang, Yichen Yang, Yang Li, Hongru Shen, Kexin Chen, Xiangchun Li

{"title":"Large language models enable tumor-type classification and localization of cancers of unknown primary from genomic data.","authors":"Jilei Liu, Meng Yang, Yajing Bi, Junqing Zhang, Yichen Yang, Yang Li, Hongru Shen, Kexin Chen, Xiangchun Li","doi":"10.1016/j.xcrm.2025.102332","DOIUrl":"10.1016/j.xcrm.2025.102332","url":null,"abstract":"Tumor-type classification is critical for effective cancer treatment, yet current methods based on genomic alterations lack flexibility and have limited performance. Here, we introduce OncoChat, an artificial intelligence (AI) model designed to classify 69 tumor types by integrating diverse genomic alterations. Developed on genomic data from 158,836 tumors sequenced with targeted cancer gene panels, OncoChat demonstrates superior performance, achieving a micro-averaged precision-recall area under the curve (PRAUC) of 0.810 (95% confidence interval [CI], 0.803-0.816), accuracy of 0.774, and an F1 score of 0.756, outperforming baseline methods. In a cancer of unknown primary (CUP) dataset of 26 cases whose types were subsequently confirmed, OncoChat correctly identified 22 cases. In two larger CUP datasets (n = 719 and 158), tumor types predicted by OncoChat were associated with survival outcomes and mutation profiles consistent with those of known tumor types. OncoChat offers promising potential for clinical decision support, particularly in managing patients with CUP.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102332"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients. 气管插管危重病人肺病毒会聚先于医院获得性肺炎。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-09-05 DOI: 10.1016/j.xcrm.2025.102289

Hussein Anani, Grégory Destras, Simon Bulteau, Louise Castain, Quentin Semanas, Gwendolyne Burfin, Mélanie Petrier, Florian P Martin, Cecile Poulain, Robert P Dickson, Céline Bressollette-Bodin, Antoine Roquilly, Laurence Josset

{"title":"Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients.","authors":"Hussein Anani, Grégory Destras, Simon Bulteau, Louise Castain, Quentin Semanas, Gwendolyne Burfin, Mélanie Petrier, Florian P Martin, Cecile Poulain, Robert P Dickson, Céline Bressollette-Bodin, Antoine Roquilly, Laurence Josset","doi":"10.1016/j.xcrm.2025.102289","DOIUrl":"10.1016/j.xcrm.2025.102289","url":null,"abstract":"Hospital-acquired pneumonia (HAP) is one of the most common nosocomial infections, leading to significant morbidity and mortality in critically ill patients. HAP is previously associated with dysbiosis of the microbiota. However, the composition of the lung virome and its role in HAP pathogenesis remain unclear. Here, we longitudinally analyze the endotracheal virome in 87 critically ill patients, including 48 with HAP. Within the virome dominated by Caudoviricetes, a decrease in viral beta-diversity toward a bacteriophage-dominated signature and a distinct viral-bacterial interactome is observed 5-4 days before HAP onset. Lung virome composition, viral convergence before HAP onset, and conservation of 18% of the bacteriophage signature are validated in an external cohort of 40 patients. In silico causal inference further identifies bacteriophages associated with Streptococcus and Prevotella as a key regulator of HAP onset. These findings suggest an uncovered pathophysiological mechanism of HAP with virome involvement in lung microbiota dysbiosis. The discovery and validation studies are registered at ClinicalTrials.gov (NCT02003196 and NCT04793568).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102289"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy. 具有超长药物靶点停留时间的ENPP1抑制剂作为先天免疫检查点阻断癌症治疗。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-09-05 DOI: 10.1016/j.xcrm.2025.102336

Songnan Wang, Randolph M Johnson, Jacqueline A Carozza, Daniel Fernandez, Jan Scicinski, Neil A Verity, Rachel Mardjuki, Xujun Cao, Yingjie Guo, Jacqueline Papkoff, Nigel Ray, Lingyin Li

{"title":"ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy.","authors":"Songnan Wang, Randolph M Johnson, Jacqueline A Carozza, Daniel Fernandez, Jan Scicinski, Neil A Verity, Rachel Mardjuki, Xujun Cao, Yingjie Guo, Jacqueline Papkoff, Nigel Ray, Lingyin Li","doi":"10.1016/j.xcrm.2025.102336","DOIUrl":"10.1016/j.xcrm.2025.102336","url":null,"abstract":"Only one in five patients respond to immune checkpoint inhibitors, which primarily target adaptive immunity. Ectonucleotide pyrophosphatase/phophodiesterase 1 (ENPP1), the dominant hydrolase of 2'3'-cyclic-GMP-AMP (cGAMP) that suppresses downstream stimulator of interferon genes (STING) signaling, has emerged as a promising innate immunotherapy target. However, existing ENPP1 inhibitors have been optimized for prolonged systemic residence time rather than effective target inhibition within tumors. Here, we report the characterization of STF-1623, a highly potent ENPP1 inhibitor with an exceptionally long tumor residence time despite rapid systemic clearance, enabled by its high ENPP1 binding affinity and slow dissociation rate. We show that membrane-bound ENPP1 on tumor cells, not the abundant soluble ENPP1 in serum, drives tumor progression. Consequently, STF-1623 unleashes anti-tumor immunity to produce robust anti-tumor and anti-metastatic effects across multiple tumor models. Conceptually, this work establishes a noncovalent small-molecule inhibitor of ENPP1 with ultralong drug-target engagement as a safe and precise strategy to activate STING within tumors.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102336"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid and sensitive acute leukemia classification and diagnosis platform using deep learning-assisted SERS detection. 基于深度学习辅助SERS检测的急性白血病快速敏感分型诊断平台。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-09-08 DOI: 10.1016/j.xcrm.2025.102320

Dongjie Zhang, Zhaoyang Cheng, Yali Song, Huandi Li, Lin Shi, Nan Wang, Yingwen Peng, Renan Chen, Nianzheng Sun, Min Han, Fengjiao Hu, Chuntao Zong, Rui Zhang, Si Chen, Conghui Zhu, Xiaoli Zhang, Xiaobo Li, Xiaopeng Ma, Changbei Shi, Xiaofei Zhang, Rui Liu, Ziqi Ren, Lin Wang, Qi Zeng, Tingting Zeng, Xueli Chen

{"title":"Rapid and sensitive acute leukemia classification and diagnosis platform using deep learning-assisted SERS detection.","authors":"Dongjie Zhang, Zhaoyang Cheng, Yali Song, Huandi Li, Lin Shi, Nan Wang, Yingwen Peng, Renan Chen, Nianzheng Sun, Min Han, Fengjiao Hu, Chuntao Zong, Rui Zhang, Si Chen, Conghui Zhu, Xiaoli Zhang, Xiaobo Li, Xiaopeng Ma, Changbei Shi, Xiaofei Zhang, Rui Liu, Ziqi Ren, Lin Wang, Qi Zeng, Tingting Zeng, Xueli Chen","doi":"10.1016/j.xcrm.2025.102320","DOIUrl":"10.1016/j.xcrm.2025.102320","url":null,"abstract":"Rapid identification and accurate diagnosis are critical for individuals with acute leukemia (AL). Here, we propose a combined deep learning and surface-enhanced Raman scattering (DL-SERS) classification strategy to achieve rapid and sensitive identification of AL with various subtypes and genetic abnormalities. More than 390 of cerebrospinal fluid (CSF) samples are collected as targets, encompassing healthy control, AL patients, and individuals with other diseases. Sensitive SERS detection could be achieved within 5 min, using only 0.5 μL volume of CSF. Through integrated feature fusion (1D spectra and 2D image) with a transformer model, the classification method is developed to screen and diagnose AL patients, demonstrating exceptional classification performances of accuracy, sensitivity, specificity, or reliability. Also, this approach demonstrates remarkable versatility and could be extended to the classifications of meningitis diseases. The sensitive DL-SERS classification platform has the potential to be a powerful auxiliary in vitro diagnostic tool.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102320"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade. 调节纤维连接蛋白细胞外基质增强免疫检查点阻断的抗肿瘤效果。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-09-08 DOI: 10.1016/j.xcrm.2025.102322

Kabir A Khan, Maresa Caunt Mitzner, William Cruz-Munoz, Grant Li, Patricia Himmels, Ping Xu, Hung Yang Kuo, Raj Jesudason, Alvin Gogineni, Robby Weimer, Annabelle Chow, Robert Piskol, Iacovos P Michael, Weilan Ye, Robert S Kerbel

{"title":"Modulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade.","authors":"Kabir A Khan, Maresa Caunt Mitzner, William Cruz-Munoz, Grant Li, Patricia Himmels, Ping Xu, Hung Yang Kuo, Raj Jesudason, Alvin Gogineni, Robby Weimer, Annabelle Chow, Robert Piskol, Iacovos P Michael, Weilan Ye, Robert S Kerbel","doi":"10.1016/j.xcrm.2025.102322","DOIUrl":"10.1016/j.xcrm.2025.102322","url":null,"abstract":"The success of immune checkpoint inhibitors is limited by multiple factors, including poor T cell infiltration and function within tumors, partly due to a dense extracellular matrix (ECM). Here, we investigate modulating the ECM by targeting integrin α5β1, a major fibronectin-binding and organizing integrin, to improve immunotherapy outcomes. Use of a function-blocking murinized α5β1 antibody reduces fibronectin fibril formation, enhances CD8+ T cell transendothelial migration, increases vascular permeability, and decreases vessel-associated collagen. These changes culminate in improving the effectiveness of PD-L1 blockade, alone or with chemotherapy, in the E0771 breast cancer model. Clinically, high integrin alpha 5 (ITGA5) expression correlates with worse survival in patients treated with atezolizumab as monotherapy or combined with chemotherapy or anti-angiogenic therapies in numerous clinical trials. Overall, our studies suggest that ECM-modulating approaches could be used as a future strategy to increase the proportion of patients who respond to immune checkpoint inhibition and other immunotherapies.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102322"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomimetic nanoimmunotherapy boosts spatiotemporal PANoptosis and reshapes desmoplastic tumor microenvironment. 仿生纳米免疫治疗可促进时空泛光状态，重塑肿瘤微环境。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-21 DOI: 10.1016/j.xcrm.2025.102312

Hui Huang, Zebin Xiao, Wei Feng, Xinran Song, Liang Chen, Lili Huang, Li Ding, Yu Chen

{"title":"Biomimetic nanoimmunotherapy boosts spatiotemporal PANoptosis and reshapes desmoplastic tumor microenvironment.","authors":"Hui Huang, Zebin Xiao, Wei Feng, Xinran Song, Liang Chen, Lili Huang, Li Ding, Yu Chen","doi":"10.1016/j.xcrm.2025.102312","DOIUrl":"10.1016/j.xcrm.2025.102312","url":null,"abstract":"Dendritic cell (DC)-based vaccines for solid tumors face major challenges, including limited tumor-specific antigens and immunosuppressive stroma. Here, we present a therapeutic nanovaccine (UCNP@MOF@MI@FM [UMMF]) composed of a DC/tumor fused cytomembrane-coated UCNP@MOF nanoparticle, co-loaded with a MutT homolog 1 (MTH1) inhibitor and combined with tetrahydrobiopterin (BH4). The fused membrane facilitates dual targeting to tumors and lymph nodes while enabling broad-spectrum tumor antigen presentation. Upon near-infrared (NIR) irradiation, upconversion-triggered reactive oxygen species (ROS) generation and MTH1 inhibition synergistically induce immunogenic PANoptosis, releasing antigens and promoting DCs maturation. Simultaneously, ROS remodels the tumor stroma by depleting collagen and cancer-associated fibroblasts, enhancing T cell infiltration. BH4 counteracts IDO-mediated kynurenine accumulation, reversing immune tolerance and restoring T cell function. This multifunctional platform integrates tumor cell killing, immune priming, and stromal reprogramming, resulting in robust antitumor immunity, reduced relapse, and metastasis suppression. UMMF offers a promising strategy for precision nanoimmunotherapy through controlled PANoptosis and microenvironment modulation.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102312"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis. PDE7A抑制通过减弱新的嘧啶生物合成来抑制三阴性乳腺癌。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 DOI: 10.1016/j.xcrm.2025.102356

Parmanand Malvi, Suresh Bugide, Roshan Dutta, Kiran Kumar Reddi, Yvonne J K Edwards, Kamaljeet Singh, Romi Gupta, Narendra Wajapeyee

{"title":"PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis.","authors":"Parmanand Malvi, Suresh Bugide, Roshan Dutta, Kiran Kumar Reddi, Yvonne J K Edwards, Kamaljeet Singh, Romi Gupta, Narendra Wajapeyee","doi":"10.1016/j.xcrm.2025.102356","DOIUrl":"10.1016/j.xcrm.2025.102356","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, associated with poor response to therapies and high mortality. We identify that phosphodiesterase 7A (PDE7A) is overexpressed in the majority of TNBCs, and a higher level of PDE7A associates with poor prognosis. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway, via the transcription factor IRF1, stimulates the expression of PDE7A in TNBC cells. PDE7A inhibition attenuates TNBC growth in both cell culture and mouse models of TNBC. Inhibition of PDE7A suppresses de novo pyrimidine biosynthesis, in part through the downregulation of the enzyme dihydroorotate dehydrogenase (DHODH). DHODH suppression attenuates TNBC tumor growth, mirroring the effects of PDE7A inhibition, and ectopic DHODH expression rescues PDE7A-inhibition-induced tumor suppression. Pharmacological co-targeting of PDE7A and DHODH potently inhibits TNBC tumor growth and metastasis. These findings identify the PDE7A → DHODH →de novo pyrimidine biosynthesis pathway as a key driver of TNBC, offering additional therapeutic opportunities for TNBC patients.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 9","pages":"102356"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis. 炎症重编程和免疫调节：动脉粥样硬化的新一代治疗方法。

IF 10.6 1区医学

Cell Reports Medicine Pub Date : 2025-09-16 Epub Date: 2025-08-08 DOI: 10.1016/j.xcrm.2025.102288

Robin P Choudhury, Rupen Hargreaves, Jason Chai, Edward A Fisher

{"title":"Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.","authors":"Robin P Choudhury, Rupen Hargreaves, Jason Chai, Edward A Fisher","doi":"10.1016/j.xcrm.2025.102288","DOIUrl":"10.1016/j.xcrm.2025.102288","url":null,"abstract":"The current generation of highly successful atherosclerosis treatments, such as low-density lipoprotein (LDL)-cholesterol reduction, blood pressure management, and smoking cessation, has largely focused on ameliorating factors perceived to drive incident disease and its complications. The adverse contributions of these factors have typically been identified through epidemiological studies. The therapeutic strategies that arose in response focused on risk factors for disease development and tended to overlook the fact that patients already have established disease, by the time of presentation. However, by capitalizing on contemporary biological knowledge and technologies, it is becoming increasingly possible to shift from a model based on population-derived risk factor management to next-generation treatments (including monoclonal antibodies, small interfering RNA [siRNA], mRNA, epigenetic reprogramming, and gene editing) for atherosclerosis that are tailored to patient-level disease processes, informed by mechanistic characterization, offer potential to reverse or regress disease, and incorporate systems-level interventions that extend beyond the atherosclerotic plaque.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102288"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0