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Immunotherapy has demonstrated benefit across multiple cancers, yet its effectiveness in brain malignancies remains constrained. This review connects circadian regulation with immunotherapy precision, assessing how circadian control shapes immune responses, cell localization, and functional phenotypes, and how circadian dysregulation alters anti-cancer immunity.",{"@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":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/integration-of-circadian-rhythms-and-immunotherapy-for-enhanced-precision-in-brain-cancer-treatment/329285/",{"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/integration-of-circadian-rhythms-and-immunotherapy-for-enhanced-precision-in-brain-cancer-treatment/329285.png","ImageObject",300,407,{"name":92,"@type":93},"Eden","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-14","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How do circadian rhythms affect brain cancer and cancer vulnerability?","Question",{"text":113,"@type":114},"Circadian rhythms regulate (patho)physiological processes, and disruptions are linked to heightened cancer vulnerability. The review emphasizes that misalignment of circadian-driven cellular processes can affect anti-cancer immunity and related outcomes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is the relationship between circadian regulation and immunotherapy precision?",{"text":118,"@type":114},"The review explains that aligning immunotherapy with the body’s internal clock can improve precision. It evaluates how circadian regulation of immune responses—including cell localization and functional phenotype—can influence immunotherapeutic effectiveness in brain cancer.",{"name":120,"@type":111,"acceptedAnswer":121},"Which immunotherapeutic strategies for brain cancer are discussed?",{"text":122,"@type":114},"The review analyzes current immunotherapeutic approaches including immune checkpoint blockades and adoptive cellular therapies, as well as other novel strategies. It further proposes future directions such as chronotherapy and personalized treatment schedules.","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},329285,1790362812,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"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,"preview_page_count":4},1374391974468,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review   \nIntegration of circadian rhythms and immunotherapy for enhanced precision in brain cancer treatment  \nMatthias Quist,a,e Maas van Os,a,e Linda W. van Laake,b,c Niels Bovenschen,a,d,e and Sandra Crnkoa,e,∗  \naDepartment of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands  \nbDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Centre Utrecht, Utrecht, the Netherlands cRegenerative Medicine Centre and Circulatory Health Research Centre, University Medical Centre Utrecht, Utrecht, the Netherlands dCentre for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands  \nSummary  \nCircadian rhythms significantly impact (patho)physiological processes, with disruptions linked to neurodegenerative diseases and heightened cancer vulnerability. While immunotherapy has shown promise in treating various cancers, its efficacy in brain malignancies remains limited. This review explores the nexus of circadian rhythms and immunotherapy in brain cancer treatment, emphasising precision through alignment with the body’s internal clock. We evaluate circadian regulation of immune responses, including cell localisation and functional phenotype, and discuss how circadian dysregulation affects anti-cancer immunity. Additionally, we analyse and assess the effectiveness of current immunotherapeutic approaches for brain cancer including immune checkpoint blockades, adoptive cellular therapies, and other novel strategies. Future directions, such as chronotherapy and personalised treatment schedules, are proposed to optimise immunotherapy precision against brain cancers. Overall, this review provides an understanding of the often-overlooked role of circadian rhythms in brain cancer and suggests avenues for improving immunotherapeutic outcomes.  \nCopyright © 2024 The Author(s) . Published by Elsevier B.V. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).  \nKeywords: Circadian rhythms; Brain cancer; Immune system; Immunotherapy; Immune checkpoints; Adoptive cellular therapy; Chronomodulated therapy  \neBioMedicine 2024;109: 105395 Published Online xxx [https://doi.org/10](https://doi.org/10) . 1016/j.ebiom.2024 . 105395  \nIntroduction  \nIn 2017 Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded with the Nobel Prize for their discovery of the molecular components that comprise the biological clock.1–4 Their research was pivotal in the uncovering of the role of circadian rhythms in physiology and pathophysiology. Nowadays, it is established that circadian (Latin “circa diem” = about a day) rhythms are an outward manifestation of an internal timing system, which is crucial for maintaining homeostatic balance in organisms.  \nCircadian rhythms at the molecular level are generated by a core molecular clock, which consists of an evolutionarily conserved transcriptional-translational feedback loop (TTFL; Fig. 1) .5 The molecular clock mechanism comprises intertwined positive and negative feedback loops. At the core, the transcriptional activators circadian locomotor output cycles kaput (CLOCK; and its paralog, NPAS2) and brain and muscle ARNT-Like 1 (BMAL1), form heterodimers that bind to enhancer box elements (E-boxes) of cryptochrome  \n*Corresponding authors. Sandra Crnko, PhD Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.  \nE-mail address: [s.crnko@umcutrecht.nl](s.crnko@umcutrecht.nl) (S. Crnko). eThese authors contributed equally.  \n(CRY1/2), period (PER1/2/3) and tyrosine-protein kinase transmembrane receptor RORα/β/γ and REVERBα/β, thereby stimulating their transcription.5,6 Subsequently, PER/CRY heterodimers accumulate and inhibit BMAL1/CLOCK activity. RORα/β/γ and REVERBα/β compete for binding to ROR response element (RORE), a promotor for BMAL1, leading ei","cbCaigqDITYeliDk","https://ap.wps.com/l/cbCaigqDITYeliDk","pdf",1562783,14,"English","# Summary\n# Introduction\n## Molecular basis of circadian rhythms\n## Core clock machinery in the brain\n# Overview of the feedback loops\n## Clock-controlled gene expression across 24 h","[{\"question\":\"How do circadian rhythms affect brain cancer and cancer vulnerability?\",\"answer\":\"Circadian rhythms regulate (patho)physiological processes, and disruptions are linked to heightened cancer vulnerability. The review emphasizes that misalignment of circadian-driven cellular processes can affect anti-cancer immunity and related outcomes.\"},{\"question\":\"What is the relationship between circadian regulation and immunotherapy precision?\",\"answer\":\"The review explains that aligning immunotherapy with the body’s internal clock can improve precision. It evaluates how circadian regulation of immune responses—including cell localization and functional phenotype—can influence immunotherapeutic effectiveness in brain cancer.\"},{\"question\":\"Which immunotherapeutic strategies for brain cancer are discussed?\",\"answer\":\"The review analyzes current immunotherapeutic approaches including immune checkpoint blockades and adoptive cellular therapies, as well as other novel strategies. It further proposes future directions such as chronotherapy and personalized treatment schedules.\"}]","Integration of circadian rhythms and immunotherapy for enhanced precision in brain cancer treatment | PDF",1789983441,35]