[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-368475-105":59,"doc-detail-368475-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","actionable-heterogeneity-of-hepatocellular-carcinoma-therapy-induced-senescence","Actionable heterogeneity of hepatocellular carcinoma - therapy-induced senescence","","Therapy-induced senescence (TIS) induces stable cell-cycle arrest in cancer cells and can enable immune control through a senescence-associated secretory phenotype (SASP). In hepatocellular carcinoma (HCC), despite extensive work on TIS-based therapeutic applicability, a complete understanding of which senescence features expose vulnerabilities for immunotherapies remains limited. Systematic studies were conducted to characterize actionable and shared SASP or other TIS-associated molecular parameters in human HCC models. TIS inducers including etoposide and alisertib, as well as CX5461, were compared for effects on SASP, surfaceome, and innate immune clearance. All compounds induced metastasis-related surface antigens and immunotherapeutically tractable targets such as CD95 (Fas), CD276 (B7-H3), and CD340 (Her2). In multiple HCC cell lines and public datasets, alisertib, etoposide, and CX5461 generated senescent HCC states susceptible to targeting by T-cell-engaging bispecific antibodies or CAR NK cells, supporting the exploitation of heterogeneous but selective senescence features across immunotherapy approaches.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/actionable-heterogeneity-of-hepatocellular-carcinoma-therapy-induced-senescence/368475/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/actionable-heterogeneity-of-hepatocellular-carcinoma-therapy-induced-senescence/368475.png","ImageObject",300,407,{"name":92,"@type":93},"Sophia Brooks","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",18,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is therapy-induced senescence (TIS) in cancer cells?","Question",{"text":113,"@type":114},"TIS is a stable cell-cycle arrest in cancerous cells. It can favor immune control by engaging a senescence-associated secretory phenotype (SASP).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which TIS inducers and immune-relevant antigens are studied in hepatocellular carcinoma?",{"text":118,"@type":114},"The study compares etoposide, alisertib, and the TIS inducer CX5461. It reports induction of immunotherapeutically tractable antigens including CD95 (Fas), CD276 (B7-H3), and CD340 (Her2).",{"name":120,"@type":111,"acceptedAnswer":121},"How do senescent HCC cells become targets for immunotherapies?",{"text":122,"@type":114},"Senescent HCC cells rendered by these compounds show susceptibility to targeting by T-cell-engaging bispecific antibodies or CAR NK cells, based on actionable and shared senescence-associated molecular features.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},368475,1790242986,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962084925636,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Cancer Immunology, Immunotherapy (2025) 74:207 [https://doi.org/10.1007/s00262-025-04060-w](https://doi.org/10.1007/s00262-025-04060-w)  \nActionable heterogeneity of hepatocellular carcinoma  \ntherapy‑induced senescence  \nPujan Engels1,2 · Andras Szolek1 · Sebastian Hörner3 · Georgios Vavouras Syrigos4,5 · Kim Hebbel1 ·  \nMichelle Schmidtke1 · Min Zhou1 · Maria Mateo‑Tortola1 · Caroline Schönfeld1 · Sylwia Anna Stefanczyk3 · Katharina Wolter2,6,7 · Sepideh Babaei8,9,10,11 · Michael Schindler4,5 · Manfred Claassen8,9,10,11 · Daniel Dauch2,6,7 · Lars Zender2,6,7 · Ana Tapía‑Abellán1,2 · Alexander N. R. Weber1,2,7,12  \nReceived: 8 July 2024 / Accepted: 14 April 2025 / Published online: 15 May 2025 © The Author(s) 2025  \nAbstract  \nTherapy-induced senescence (TIS) is a stable cell cycle arrest in cancerous cells favoring immune control upon immune cell recruitment and activation via a senescence-associated secretory phenotype (SASP) . Numerous studies have investigated the therapeutic applicability of TIS in hepatocellular carcinoma (HCC), a frequent cancer with high morbidity and mortality. Despite these efforts, a comprehensive understanding of how TIS may expose vulnerabilities specifically for immunotherapies, a potent means of cancer therapy, in HCC remains incomplete. Therefore, we conducted systematic studies to carefully characterize actionable and shared SASP-or other senescence-associated molecular parameters of TIS. We systematically compared the TIS inducers, etoposide and alisertib with a novel TIS inducer, CX5461, for their effects on SASP, surfaceome and innate immune clearance of representative human HCC cell lines. Surprisingly, all three compounds induced both metastasis surface antigens but also immunotherapeutically tractable antigens like CD95 (Fas), CD276 (B7-H3) and CD340 (Her2). This was verified in four representative HCC cell lines and publicly available datasets of HCC. Interestingly, alisertib, etoposide and CX5461 rendered senescent HCC vulnerable to be targeted by either T-cell-engaging bispecific antibodies or CAR NK cells. Collectively, our study indicates that heterogenous, but selective features of HCC senescence may be exploited by different immunotherapeutic approaches.  \nKeywords Senescence · Hepatocellular carcinoma · Immunotherapy · Immunology  \n* Alexander N. R. Weber [alexander.weber@uni-tuebingen.de](alexander.weber@uni-tuebingen.de)  \n1 Department of Innate Immunity, Institute of Immunology, University of Tübingen, Tübingen, Germany  \n2 iFIT Cluster of Excellence 2180,‘Image-Guided and Functionally Instructed Tumor Therapies’, University of Tübingen, Tübingen, Germany  \n3 Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany  \n4 Department of Medical Virology, Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany  \n5 DZIF Partner Site Tübingen, Tübingen, Germany  \n6 Department of Medical Oncology and Pneumology, University Hospital Tübingen, Tübingen, Germany  \n7 German Cancer Research Consortium (DKTK), Partner Site Tübingen, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany  \n8 Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany  \n9 Department of Computer Science, University of Tübingen, Tübingen, Germany  \n10 M3 Research Center, University Hospital Tübingen, Tübingen, Germany  \n11 Institute for Bioinformatics and Medical Informatics, University of Tübingen, Tübingen, Germany  \n12 Cluster of Excellence 2124 CMFI, Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany  \nAbbreviations  \nCAR  \nEMT  \nFDG  \nGSEA  \nHCC  \nMFI  \nSASPSA-β-Gal SASome TIS  \nChimeric antigen receptor  \nEpithelial-mesenchymal transition Fluorescein-Di-β-D-galactopyranoside Gene set enrichment analysis Hepatocellular carcinoma  \nMedian fluorescent intensity  \nSenescence-ass","cbCaiaH5fbD2ykLm","https://ap.wps.com/l/cbCaiaH5fbD2ykLm","pdf",2248830,13,"English","# Abstract\n# Keywords","[{\"question\":\"What is therapy-induced senescence (TIS) in cancer cells?\",\"answer\":\"TIS is a stable cell-cycle arrest in cancerous cells. It can favor immune control by engaging a senescence-associated secretory phenotype (SASP).\"},{\"question\":\"Which TIS inducers and immune-relevant antigens are studied in hepatocellular carcinoma?\",\"answer\":\"The study compares etoposide, alisertib, and the TIS inducer CX5461. It reports induction of immunotherapeutically tractable antigens including CD95 (Fas), CD276 (B7-H3), and CD340 (Her2).\"},{\"question\":\"How do senescent HCC cells become targets for immunotherapies?\",\"answer\":\"Senescent HCC cells rendered by these compounds show susceptibility to targeting by T-cell-engaging bispecific antibodies or CAR NK cells, based on actionable and shared senescence-associated molecular features.\"}]","Actionable heterogeneity of hepatocellular carcinoma - therapy-induced senescence | PDF",1790177158,33]