[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-364803-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-364803-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","cyclin-e1-overexpression-triggers-interferon-signaling-and-is-associated-with-antitumor-immunity-in-breast-cancer","Cyclin E1 overexpression triggers interferon signaling and is associated with antitumor immunity in breast cancer","","Cyclin E1 overexpression drives oncogenesis through altered DNA replication and genomic instability, potentially engaging immune signaling through cytoplasmic DNA. The study evaluates how cyclin E1 expression influences tumor immunity and how it relates to outcomes after immune checkpoint inhibitor therapy in breast cancer. Tissue microarrays and patient data from 398 cases are analyzed alongside public genomic datasets and three immunotherapy trials, supported by cell line models with inducible cyclin E1.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/cyclin-e1-overexpression-triggers-interferon-signaling-and-is-associated-with-antitumor-immunity-in-breast-cancer/364803/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/cyclin-e1-overexpression-triggers-interferon-signaling-and-is-associated-with-antitumor-immunity-in-breast-cancer/364803.png","ImageObject",300,407,{"name":42,"@type":43},"Riley","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does the study address about Cyclin E1 in breast cancer?","Question",{"text":63,"@type":64},"It investigates whether cyclin E1 overexpression triggers inflammatory/interferon signaling, influences tumor immunity, and affects response to immune checkpoint inhibitors, which has remained unclear.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the researchers assess the relationship between cyclin E1 and immune responses?",{"text":68,"@type":64},"They analyzed tissue microarrays and clinical outcomes from 398 breast cancer patients for cyclin E1 expression, survival, and immune cell infiltration, and they used public genomic datasets plus three immunotherapy trials. They also used breast cancer cell lines with inducible cyclin E1 to test inflammatory signaling effects.",{"name":70,"@type":61,"acceptedAnswer":71},"What are the key findings regarding interferon signaling and immunotherapy response?",{"text":72,"@type":64},"Higher cyclin E1 expression correlates with increased infiltration of T cells, B cells, and natural killer cells and activation of interferon-related pathways. In clinical trials, higher cyclin E1 expression or CCNE1 amplification is associated with better immunotherapy response, supported mechanistically by micronuclei formation and innate immune activation.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},364803,1790241534,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":113},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Open access Original research  \n Cyclin E1 overexpression triggers  \ninterferon signaling and is associated with antitumor immunity in breast cancer  \nShibo Yu,1 Chantal Stappenbelt,2 Mengting Chen,2,3 Mirte Dekker,1 Arkajyoti Bhattacharya,2 Tineke van der Sluis,1 Mieke C Zwager,1 Carolien P Schröder,2,4 Rudolf S N Fehrmann,2 Marcel A T M van Vugt,2 Bert van der Vegt  1  \nTo cite: Yu S, Stappenbelt C, Chen M, et al. Cyclin E1 overexpression triggers interferon signaling and is associated with antitumor immunity in breast  \ncancer. Journal for ImmunoTherapy of Cancer 2025;13:e009239 . doi:10 . 1136/ jitc-2024-009239  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2024-009239](jitc-2024-009239)) .  \nSY, CS and MC contributed equally.  \nAccepted 03 March 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Bert van der Vegt; [b.van.der.vegt@umcg.nl](b.van.der.vegt@umcg.nl)  \nProfessor Marcel A T M van Vugt; [m.vugt@umcg.nl](m.vugt@umcg.nl)  \nABSTRACT  \nBackground Cyclin E1 overexpression drives oncogenesisin several cancers through deregulation of DNA replication and induction of genomic instability, which may potentially trigger immune signaling via cytoplasmic DNA. However, the effects of cyclin E1 overexpression on tumor immunity and its effects on the response to immune checkpoint inhibitors remain largely unclear.  \nMethods Tissue microarrays and clinical outcomes of 398 patients with breast cancer were analyzed to explore the correlation between cyclin E1 expression, patient survival, and immune cell infiltration using immunohistochemistry. Genomic data from publicly available data sets and three clinical trials evaluating immunotherapy were assessed to measure the impact of cyclin E1 expression on the immune cells in the tumor microenvironment and response to immunotherapy in patients with breast cancer. In addition, breast cancer cell lines with inducible cyclin E1 overexpression were employed to analyze the effects of cyclin E1 on inflammatory signaling.  \nResults Increased cyclin E1 expression in breast cancer was positively correlated with immune cell infiltration, including T cells, B cells, and natural killer cells, and activation of interferon-related pathways. Importantly, higher cyclin E1 expression or CCNE1 amplification was associated with better response to immunotherapy in three clinical trials. Mechanistically, cyclin E1 overexpression resulted in micronuclei formation and activation of innate immune signaling, resulting in increased immune cell migration.  \nConclusions Our data show that cyclin E1 overexpression associate with antitumor immunity through activation of innate inflammatory signaling and warrants investigation into amplification or overexpression of cyclin E1 in identifying patients with breast cancer eligible for immunotherapy.  \nBACKGROUND  \nOne in eight cancer cases diagnosed globally concerns breast cancer, making it one of the most frequently diagnosed cancer types.1 Over the recent years, immune checkpoint  \nWHAT IS ALREADY KNOWN ON THIS TOPIC  \n\n| ⇒ CCNE1 amplification, as one of the major sources of replication stress in cancer cells, is known to induce genomic instability. Genomic instability can trigger immune signaling via cytoplasmic DNA. However, whether cyclin E1 overexpression triggers inflammatory signaling and has effects on tumor immunity and response to immune checkpoint inhibitors inpatients with breast cancer remains largely unclear.\u003Cbr>WHAT THIS STUDY ADDS |\n| --- |\n| ⇒ Increased cyclin E1 expression in breast cancer positively correlates with immune cell infiltration and better response to immunotherapy.\u003Cbr>⇒ Cyclin E1 overexpression results in micronuclei for","cbCaikZeNDWRZfTH","https://ap.wps.com/l/cbCaikZeNDWRZfTH","pdf",5559044,12,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# What is already known on this topic\n# What this study adds\n# How this study might affect research, practice or policy","[{\"question\":\"What question does the study address about Cyclin E1 in breast cancer?\",\"answer\":\"It investigates whether cyclin E1 overexpression triggers inflammatory/interferon signaling, influences tumor immunity, and affects response to immune checkpoint inhibitors, which has remained unclear.\"},{\"question\":\"How did the researchers assess the relationship between cyclin E1 and immune responses?\",\"answer\":\"They analyzed tissue microarrays and clinical outcomes from 398 breast cancer patients for cyclin E1 expression, survival, and immune cell infiltration, and they used public genomic datasets plus three immunotherapy trials. They also used breast cancer cell lines with inducible cyclin E1 to test inflammatory signaling effects.\"},{\"question\":\"What are the key findings regarding interferon signaling and immunotherapy response?\",\"answer\":\"Higher cyclin E1 expression correlates with increased infiltration of T cells, B cells, and natural killer cells and activation of interferon-related pathways. In clinical trials, higher cyclin E1 expression or CCNE1 amplification is associated with better immunotherapy response, supported mechanistically by micronuclei formation and innate immune activation.\"}]","Cyclin E1 overexpression triggers interferon signaling and is associated with antitumor immunity in breast cancer | PDF",1790159114]