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Pancreatic cancers are largely resistant to single-agent immunotherapy, making immune-resistance mechanisms and combination strategies critical. This study analyzes BAP1’s regulation of HSF1 and its impact on immune therapy sensitivity.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/bap1-regulates-hsf1-activity-and-cancer-immunity-in-pancreatic-cancer/332548/",{"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/bap1-regulates-hsf1-activity-and-cancer-immunity-in-pancreatic-cancer/332548.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is combination immunotherapy important in pancreatic cancer?","Question",{"text":112,"@type":113},"Most pancreatic cancers behave as immune cold tumors and do not benefit from single-agent immunotherapy. The document highlights the need for combination strategies to overcome immune resistance in PDAC patients.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does BAP1 deletion affect immune therapy response?",{"text":117,"@type":113},"BAP1 deletion contributes to immunotherapy resistance in PDAC. The study attributes this to BAP1’s suppression of HSF1 transcriptional activity and related downstream interactions.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does SIRT1 inhibition play in BAP1-deficient PDAC?",{"text":121,"@type":113},"Targeted inhibition of SIRT1 reverses immune insensitivity in a BAP1-deficient PDAC mouse model, indicating a synergistic therapeutic potential with anti-PD-1 therapy.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332548,1790559809,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Yuan et al. Journal of Experimental & Clinical Cancer Research (2024) 43:275 [https://doi.org/10.1186/s13046-024-03196-4](https://doi.org/10.1186/s13046-024-03196-4)  \nJournal of Experimental & Clinical Cancer Research  \nRESEARCH Open Access  \nBAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer  \nWeiwei Yuan 1,2†, Qiyue Zhang2,3†, Yuhan Zhao2,3†, Wentao Xia2,3, Shilin Yin2,3, Xueyi Liang2,3, Taoyu Chen2,3, Gaofeng Li 1, Yanshen Liu4*, Zhiqiang Liu2,3* and Jinxi Huang 1*  \nAbstract  \nBackground The vast majority of pancreatic cancers have been shown to be insensitive to single-agent immunotherapy. Exploring the mechanisms of immune resistance and implementing combination therapeutic strategies are crucial for PDAC patients to derive benefits from immunotherapy. Deletion of BAP1 occurs in approximately 27% of PDAC patients and is significantly correlated with poor prognosis, but the mechanism how BAP1-deletion compromises survival of patients with PDAC remain a puzzle.  \nMethods Bap1 knock-out KPC (KrasG12D/+; LSLTrp53R172H/+; Pdx-1-Cre) mice and control KPC mice, syngeneic xenograft models were applied to analysis the correlation between BAP1 and immune therapy response in PDAC. Immunoprecipitation, RT-qPCR, luciferase and transcriptome analysis were combined to revealing potential mechanisms. Syngeneic xenograft models and flow cytometry were constructed to examine the efficacy of the inhibitor of SIRT1 and its synergistic effect with anti-PD-1 therapy.  \nResult The deletion of BAP1 contributes to the resistance to immunotherapy in PDAC, which is attributable to BAP1’s suppression of the transcriptional activity of HSF1 . Specifically, BAP1 competes with SIRT1 for binding to the K80 acetylated HSF1 . The BAP1-HSF1 interaction preserves the acetylation of HSF1-K80 and promotes HSF1-HSP70 interaction, facilitating HSF1 oligomerization and detachment from the chromatin. Furthermore, we demonstrate that the targeted inhibition of SIRT1 reverses the immune insensitivity in BAP1 deficient PDAC mouse model.  \nConclusion Our study elucidates an unrevealed mechanism by which BAP1 regulates immune therapy response in PDAC via HSF1 inhibition, and providing promising therapeutic strategies to address immune insensitivity in BAP1-deficient PDAC.  \nKeywords BRCA1 associated protein-1, Programmed death-ligand 1, Heat shock transcription factor 1, Pancreatic cancer  \n†Weiwei Yuan, Qiyue Zhang andYuhan Zhao contributed equally to this work.  \n*Correspondence:  \nYanshen Liu [liu_yanshen@hust.edu.cn](liu_yanshen@hust.edu.cn)[ ](liu_yanshen@hust.edu.cn)Zhiqiang Liu [drliuzq@hust.edu.cn](drliuzq@hust.edu.cn)[ ](drliuzq@hust.edu.cn)Jinxi Huang [zlyyhuangjinxi@zzu.edu.cn](zlyyhuangjinxi@zzu.edu.cn)  \n1Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou  \n450008, China  \n2Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China  \n3Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China  \n4Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted","cbCaia1yh1NPCXZv","https://ap.wps.com/l/cbCaia1yh1NPCXZv","pdf",7885895,16,"English","# Abstract\n## Background\n## Methods\n## Result\n## Conclusion\n# Introduction","[{\"question\":\"Why is combination immunotherapy important in pancreatic cancer?\",\"answer\":\"Most pancreatic cancers behave as immune cold tumors and do not benefit from single-agent immunotherapy. The document highlights the need for combination strategies to overcome immune resistance in PDAC patients.\"},{\"question\":\"How does BAP1 deletion affect immune therapy response?\",\"answer\":\"BAP1 deletion contributes to immunotherapy resistance in PDAC. The study attributes this to BAP1’s suppression of HSF1 transcriptional activity and related downstream interactions.\"},{\"question\":\"What role does SIRT1 inhibition play in BAP1-deficient PDAC?\",\"answer\":\"Targeted inhibition of SIRT1 reverses immune insensitivity in a BAP1-deficient PDAC mouse model, indicating a synergistic therapeutic potential with anti-PD-1 therapy.\"}]","BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer | PDF",1789998661]