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Methods: Effects were assessed on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs using Western blot, VEGFA by RT-qPCR/ELISA, and angiogenesis via immunofluorescence, supported by LUAD–HUVEC in vitro modeling. In C57BL/6 tumor-bearing mice, RT and anti-PD-L1 with or without Lenvatinib were compared by tumor growth, survival, mIHC, and flow cytometry. Results and Conclusions: Lenvatinib suppressed PD-L1/VEGFR2 signaling, reduced angiogenesis, improved survival, enhanced CD8+ activity, promoted M1-like macrophages, and lowered Tregs and microvessel density.",{"@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":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/lenvatinib-potentiates-the-antitumor-efficacy-of-combined-radiotherapy-and-pd-l1-blockade-in-lung-adenocarcinoma/444887/",{"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/lenvatinib-potentiates-the-antitumor-efficacy-of-combined-radiotherapy-and-pd-l1-blockade-in-lung-adenocarcinoma/444887.png","ImageObject",300,407,{"name":92,"@type":93},"Blue Pony","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What therapeutic combinations were evaluated in this study?","Question",{"text":112,"@type":113},"Radiotherapy and anti-PD-L1 were tested with or without Lenvatinib. The key comparison was the triple combination versus dual therapy in lung adenocarcinoma models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which molecular and cellular mechanisms were measured?",{"text":117,"@type":113},"The study assessed radiation-induced PD-L1 and VEGFR2 expression, VEGFA levels, angiogenesis, and LUAD–HUVEC crosstalk, using Western blot, RT-qPCR/ELISA, and immunofluorescence, complemented by immune profiling in vivo.",{"name":119,"@type":110,"acceptedAnswer":120},"How did Lenvatinib affect treatment efficacy and survival?",{"text":121,"@type":113},"The triple combination significantly suppressed tumor progression and extended median survival compared with dual therapy, with improved intratumoral CD8+ T-cell infiltration and cytotoxicity.","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},444887,1790983793,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"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":145,"preview_page_count":4},962090760266,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","CANCER BIOLOGY & THERAPY 2026, VOL. 27, NO. 1, 2610526  \n[https://doi.org/10.1080/15384047.2025.2610526](https://doi.org/10.1080/15384047.2025.2610526)  \nRESEARCH ARTICLE     \nLenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma  \nYudi Liua , Ling Xiaoa , Xinyu Nieb, Jiahua Lyuc, Chengxi Tanga, Linjie Lia, Xue Zhanga, Tao Lic, Jianming Huangd  and Shichuan Zhangc  \naDepartment of Radiation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People's Republic of China; bThe People's Hospital of Kaizhou District, Chongqing, People's Republic of China; cDepartment of Radiation, Radiation Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, People's Republic of China; dBiochemistry and Molecular Biology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, People's Republic of China  \nABSTRACT  \nBackground: The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized.  \nMethods: We investigated Lenvatinib’s effects on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs via Western blot, VEGFA expression via RT-qPCR/ELISA, and angiogenesis via immunofluorescence. LUAD-HUVEC crosstalk was modeled in vitro. In C57BL/6 mice bearing LUAD tumors, we evaluated the efficacy of RT and anti-PD-L1 with or without Lenvatinib, monitoring tumor growth, survival, and profiling the tumor microenvironment by mIHC and flow cytometry.  \nResults: Lenvatinib suppressed radiation-induced PD-L1 and VEGFR2 expression, inhibited angiogenesis, and disrupted HUVEC-facilitated LUAD proliferation. The triplecombination (RT + anti-PD-L1 + Lenvatinib) significantly suppressed tumor progression (P \u003C 0.05) and extended median survival (34 vs. 29.5 days, P \u003C 0.05) versus dual therapy. It also enhanced intratumoral CD8+ T-cell infiltration and cytotoxicity, promoted M1-like macrophage polarization, and reduced regulatory T cell frequency and microvessel density.  \nConclusions: Lenvatinib potentiates RT and anti-PD-L1 therapy in LUAD through dual immune-vascular modulation, supporting the clinical translation of this triplecombination strategy.  \nARTICLE HISTORY  \nReceived 14 August 2025 Revised 17 November 2025 Accepted 23 December 2025  \nKEYWORDS  \nLenvatinib; radiotherapy; PD-L1; VEGFR2; lung adenocarcinoma  \nCONTACT Jianming Huang  [wesleyhuangcn2002@163.com](wesleyhuangcn2002@163.com)  Biochemistry and Molecular Biology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South People’s Road, Chengdu, People's Republic of China; Shichuan Zhang  [zhangshichuan@scszlyy.org.cn](zhangshichuan@scszlyy.org.cn)[ ](zhangshichuan@scszlyy.org.cn) Department of Radiation, Radiation Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic, Science and Technology of China, No. 55, Section 4, South People’s Road, Chengdu, People's Republic of China  \n Supplemental data for this article can be accessed online at [https://doi.org/10.1080/15384047.2025.2610526](https://doi.org/10.1080/15384047.2025.2610526) .  \n© 2025 The Author(s) . Published with license by Taylor & Francis Group, LLC.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by","cbCainvc61WOp43f","https://ap.wps.com/l/cbCainvc61WOp43f","pdf",3472688,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Radiotherapy in lung adenocarcinoma\n## Limitations of RT and need for combinations\n## PD-L1 upregulation and immune suppression\n## Antiangiogenic strategy and translational barrier","[{\"question\":\"What therapeutic combinations were evaluated in this study?\",\"answer\":\"Radiotherapy and anti-PD-L1 were tested with or without Lenvatinib. The key comparison was the triple combination versus dual therapy in lung adenocarcinoma models.\"},{\"question\":\"Which molecular and cellular mechanisms were measured?\",\"answer\":\"The study assessed radiation-induced PD-L1 and VEGFR2 expression, VEGFA levels, angiogenesis, and LUAD–HUVEC crosstalk, using Western blot, RT-qPCR/ELISA, and immunofluorescence, complemented by immune profiling in vivo.\"},{\"question\":\"How did Lenvatinib affect treatment efficacy and survival?\",\"answer\":\"The triple combination significantly suppressed tumor progression and extended median survival compared with dual therapy, with improved intratumoral CD8+ T-cell infiltration and cytotoxicity.\"}]","Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma | PDF",1790709619,38]