[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-376352-105":3,"doc-detail-376352-en":81,"detail-sidebar-cat-0-en-105":99},{"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","cdk1213-inactivation-triggers-sting-mediated-antitumor-immunity-in-preclinical-models","CDK12/13 inactivation triggers STING-mediated antitumor immunity in preclinical models","","Inactivation of cyclin-dependent kinase 12 (CDK12) defines an immunogenic prostate cancer subtype marked by genomic instability and increased intratumoral T cell infiltration. The study demonstrates that genetic or pharmacologic inactivation of CDK12 and its paralog CDK13 robustly activates STING signaling across multiple cancer types. Cytosolic nucleic acid release upon CDK12/13 depletion or degradation triggers STING pathway activation, delays tumor growth, and synergizes with anti–PD-1 therapy, requiring STING activity and functional CD8+ T cells. Findings identify STING activation as a key driver of CD8+ infiltration and immune-hot microenvironments in CDK12-mutant cancers.",{"@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/cdk1213-inactivation-triggers-sting-mediated-antitumor-immunity-in-preclinical-models/376352/",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/cdk1213-inactivation-triggers-sting-mediated-antitumor-immunity-in-preclinical-models/376352.png","ImageObject",300,407,{"name":42,"@type":43},"Bulrr","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What effect does CDK12/13 inactivation have on STING signaling?","Question",{"text":63,"@type":64},"Genetic or pharmacologic inactivation of CDK12 and CDK13 robustly activates STING signaling across multiple cancer types by inducing cytosolic nucleic acid release.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does CDK12/13 depletion or targeted degradation impact tumor growth and therapy response?",{"text":68,"@type":64},"CDK12/13 depletion or targeted degradation delays tumor growth and synergizes with anti–PD-1 therapy in syngeneic tumor models, increasing STING activity and promoting CD8+ T cell infiltration and activation.",{"name":70,"@type":61,"acceptedAnswer":71},"Which components are required for the antitumor effects of the CDK12/13 plus anti–PD-1 combination?",{"text":72,"@type":64},"The antitumor effects require both STING signaling and functional CD8+ T cells, establishing STING activation as a key driver of the immune-hot tumor microenvironment.","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},376352,1790243471,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8",7,"The Journal of Clinical Investigation RESEAR CH ARTICLE  \nCDK12/13 inactivation triggers STING-mediated antitumor immunity in preclinical models  \nYi Bao,1,2 Yu Chang,1,2 Jean Ching-Yi Tien,1,2 Gabriel Cruz,1,2 Fan Yang,1,2 Rahul Mannan,1,2 Somnath Mahapatra,1,2 Radha Paturu,1,2 Xuhong Cao,1,2 Fengyun Su,1,2 Rui Wang,1,2 Yuping Zhang,1,2 Mahnoor Gondal,1,2,3 Jae Eun Choi,1,2 Jonathan K. Gurkan,1 Stephanie J. Miner,1,2 Dan R. Robinson,1,2 Yi-Mi Wu,1,2 Licheng Zhou,4,5 Zhen Wang,4,5 Ilona Kryczek,6,7 Xiaoju Wang,1,2,8  \nMarcin Cieslik,1,2,3 Yuanyuan Qiao,1,2,8 Alexander Tsodikov,9 Weiping Zou,1,2,6,7,8 Ke Ding,4 and Arul M. Chinnaiyan1,2,8,10,11 1Michigan Center for Translational Pathology, 2Department of Pathology, and 3Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.  \n4State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. 5International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, College of Pharmacy, Jinan University, Guangzhou, China. 6Department of Surgery, 7Center of Excellence for Cancer Immunology and Immunotherapy, 8Rogel Cancer Center, 9Department of Biostatistics, 10Howard Hughes Medical Institute, and 11Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.  \nInactivation of cyclin-dependent kinase 12 (CDK12) defines an immunogenic molecular subtype of prostate cancer characterized by genomic instability and increased intratumoral T cell infiltration. This study revealed that genetic orpharmacologic inactivation of CDK12 and its paralog CDK13 robustly activates stimulator of interferon genes (STING) signaling across multiple cancer types. Clinical cohort analysis showed that reduced CDK12/13 expression correlates with improved survival and response to immune checkpoint blockade (ICB) . Mechanistically, CDK12/13 depletion or targeted degradation induced cytosolic nucleic acid release, triggering STING pathway activation. CDK12/13 degradation delayed tumor growth and synergized with anti–PD-1 therapy in syngeneic tumor models, enhancing STING activity and promoting CD8+ T cell infiltration and activation within tumors. Notably, the antitumor effects of this combination required STING signaling and functional CD8+ T cells. These findings establish STING activation as the key driver of T cell infiltration and the immune-hot tumor microenvironment in CDK12-mutant cancers, suggesting that dual CDK12/13 inhibitors and degraders activate antitumor immunity and potentiate responses to immunotherapies.  \nIntroduction  \nThe interplay between tumor biology and the immune response has emerged as a crucial area of research in cancer therapy, particularly in the context of immune checkpoint blockade (ICB) (1, 2) . Nevertheless, a substantial proportion of patients experience resistance to ICB, either through intrinsic mechanisms within the tumor microenvironment or through acquired resistance during therapy (2, 3) . Accumulating studies have demonstrated that the stimulator of interferon (IFN) genes (STING) signaling pathway, which can be activated by cytosolic nucleic acids (4–6), plays a key role in boosting the immune response against tumors and enhancing  \nAuthorship note: YB and YC contributed equally to this work and are co–first authors. Conflict of interest: AMC is a co-founder and serves on the Scientific Advisory Board of Lynx Dx, Esanik Therapeutics, Medsyn, and Flamingo Therapeutics. AMC is a scientific consultant for EdenRoc, Proteovant, Aurigene Oncology, RAPPTA, Belharra, and Tempus. KD provides advisory services to Kinoteck Therapeutics and has received financial support from Livzon Pharmaceutical Group. WZ acts as a scientific advisor for NGM, CrownBio, Cstone, Proteovant, Hengenix, NextCure, and Intergal","cbCaieSk5bNRcw5H","https://ap.wps.com/l/cbCaieSk5bNRcw5H","pdf",14947629,17,"English","# Introduction\n## CDK12/CDK13 immunogenic subtype and T cell infiltration\n## STING pathway activation by cytosolic nucleic acids\n## Mechanistic link: RNAPII transcriptional roles and nucleic acid release\n## Therapeutic implications with anti–PD-1","[{\"question\":\"What effect does CDK12/13 inactivation have on STING signaling?\",\"answer\":\"Genetic or pharmacologic inactivation of CDK12 and CDK13 robustly activates STING signaling across multiple cancer types by inducing cytosolic nucleic acid release.\"},{\"question\":\"How does CDK12/13 depletion or targeted degradation impact tumor growth and therapy response?\",\"answer\":\"CDK12/13 depletion or targeted degradation delays tumor growth and synergizes with anti–PD-1 therapy in syngeneic tumor models, increasing STING activity and promoting CD8+ T cell infiltration and activation.\"},{\"question\":\"Which components are required for the antitumor effects of the CDK12/13 plus anti–PD-1 combination?\",\"answer\":\"The antitumor effects require both STING signaling and functional CD8+ T cells, establishing STING activation as a key driver of the immune-hot tumor microenvironment.\"}]","CDK12/13 inactivation triggers STING-mediated antitumor immunity in preclinical models | PDF",1790218323,43,{"code":4,"msg":82,"data":100},[101,105,109,113,118,123,126,131,136,139,143],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},5,"Comic",60,"comic",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},6,"Technology",50,"technology",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":124,"slug":125},40,"healthcare",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":129,"slug":130},8,"Research & Report",30,"research-report",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":134,"slug":135},9,"Religion & Spirituality",20,"religion-spirituality",{"id":134,"doc_module":4,"doc_module_name":25,"category_name":137,"show_sort_weight":134,"slug":138},"World Cup","world-cup",{"id":140,"doc_module":4,"doc_module_name":25,"category_name":141,"show_sort_weight":140,"slug":142},10,"Lifestyle","lifestyle",{"id":144,"doc_module":4,"doc_module_name":25,"category_name":145,"show_sort_weight":114,"slug":146},19,"General","general"]