[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-448510-en":3,"doc-seo-448510-105":30,"detail-sidebar-cat-0-en-105":98},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":11,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29,"preview_page_count":4},448510,2336474466412,"\tJames","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d",7,"Healthcare","OX40L and IL-2 combination strategy for gastric cancer immunotherapy","Gastric cancer remains a major global health challenge, with low remission rates largely driven by late diagnosis and an immunosuppressive tumor microenvironment that limits effective T-cell activation and costimulatory signaling. This study evaluates whether dual stimulation with interleukin-2 (IL-2) and OX40 ligand (OX40L) synergistically enhances antitumor T-cell responses. Analyses of OX40/OX40L expression in tumors and TILs were paired with in vitro testing in PBMCs and a recombinant adenoviral co-expression approach for cytotoxic potency.","OX40L and IL-2 combination strategy for gastric cancer immunotherapy  \nBenshun Hu1,2\\#, Emanuela Garbarino2\\#, Jingjing Ma3\\#, Chengyuan Yan4\\#, Junli Jia2, Hua Xie4, Lingyun Li5, Cheng Jin6, Yuzheng Xue1, Huamin Tang2,7^  \n1Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China; 2Department of Immunology, National Vaccine Innovation Platform, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China; 3Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China; 4Second Department of Bone, Jintan Hospital Affiliated to Jiangsu University, Changzhou, China; 5Deparment of Medical Genetics, Nanjing Medical University, Nanjing, China; 6Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China; 7The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, China  \nContributions: (I) Conception and design: H Tang, Y Xue, C Jin; (II) Administrative support: H Tang; (III) Provision of study materials or patients: Y Xue, C Jin; (IV) Collection and assembly of data: B Hu, E Garbarino, J Ma, C Yan, J Jia, H Xie, L Li; (V) Data analysis and interpretation: B Hu, EGarbarino, J Ma; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.  \n\\#These authors contributed equally to this work.  \nCorrespondence to: Huamin Tang, PhD. Department of Immunology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China; The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, China. Email: [htang@njmu.edu.cn](htang@njmu.edu.cn); Yuzheng Xue, PhD. Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi 214122, China. [Email: xueyz001@163.com](Email: xueyz001@163.com); Cheng Jin, PhD. Department of Gastroenterology, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi 214122, China. [Email: jingcheng1008@163.com](Email: jingcheng1008@163.com).  \nBackground: Gastric cancer (GC) remains a major global health challenge with persistently low remission rates, largely because most patients are diagnosed at advanced stages. Although chemotherapy, targeted therapy, and immune checkpoint inhibitors have achieved progress, their benefits remain limited due to the highly immunosuppressive tumor microenvironment (TME), characterized by inadequate T-cell activation and impaired costimulatory signaling. Recent genomic and single-cell studies highlight the need for strategies that can more effectively enhance antitumor immunity. Given these challenges, this study aimed to evaluate whether dual stimulation with interleukin-2 (IL-2) and OX40 ligand (OX40L) could synergistically enhance T-cell activation in GC. Specifically, we analyzed OX40/OX40L expression patterns in GC tissues and tumor-infiltrating lymphocytes (TILs), assessed the immunostimulatory effects of IL-2 and OX40L in PBMCs and TILs, and tested a recombinant adenoviral vector co-expressing IL-2 and OX40L to determine  \nits ability to potentiate T-cell-mediated cytotoxicity against primary GC tumor cells.  \nMethods: Based on preliminary analyses of The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing (scRNA-seq) data, we identified the costimulatory molecules IL-2 and OX40L as potential therapeutic targets. We collected tumor tissues and paired peripheral blood mononuclear cells (PBMCs) from 70 untreated GC patients, and used bioinformatics tools to analyze T cell subpopulations and OX40/ OX40L expression in the TME. The immunostimulatory effects of IL-2 and OX40L, used alone or in combination, were evaluated in vitro on PBMCs and TILs. A recombinant adenoviral vector co-expressing IL-2 and OX40L was also constructed to assess its pro-apoptotic effect in primary GC tumor cell cultures.  \nResults: The combination of IL-2 and OX40L significantly enhanced T cell activation in both PBMCsand TILs, and increased ","cbCaiq7x93zblDCJ","https://ap.wps.com/l/cbCaiq7x93zblDCJ","pdf",4740036,1,18,"English","en",105,"# Introduction\n## Background and rationale\n# Methods\n## Patient sampling and bioinformatics\n## In vitro and vector-based assays\n# Results\n## IL-2/OX40L synergy in T-cell activation\n# Conclusions","[{\"question\":\"Why is combination therapy with IL-2 and OX40L considered for gastric cancer immunotherapy?\",\"answer\":\"Because gastric cancer tumor microenvironments show inadequate T-cell activation and impaired costimulatory signaling, the study tests whether IL-2 and OX40L dual stimulation can synergistically enhance antitumor immunity.\"},{\"question\":\"What experiments were used to assess IL-2 and OX40L effects?\",\"answer\":\"The study analyzes OX40/OX40L expression in gastric tissues and TILs, evaluates immunostimulatory effects of IL-2 and OX40L alone or together in PBMCs and TILs, and constructs a recombinant adenoviral vector co-expressing IL-2 and OX40L.\"},{\"question\":\"What were the main findings from the IL-2/OX40L strategy?\",\"answer\":\"The IL-2 and OX40L combination significantly enhanced T-cell activation in both PBMCs and TILs and increased antitumor effector molecule expression. The adenoviral IL-2/OX40L vector effectively activated TILs, which then induced prominent apoptosis in primary gastric cancer tumor cells.\"}]","OX40L and IL-2 combination strategy for gastric cancer immunotherapy | PDF",1790727484,45,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":92,"head_meta":94,"extra_data":96,"updated_unix":97},"ox40l-and-il-2-combination-strategy-for-gastric-cancer-immunotherapy","",{"@graph":36,"@context":91},[37,54,74],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/healthcare/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/ox40l-and-il-2-combination-strategy-for-gastric-cancer-immunotherapy/448510/",4,{"url":52,"name":13,"@type":55,"image":56,"author":61,"headline":13,"publisher":63,"fileFormat":66,"inLanguage":23,"description":14,"dateModified":67,"datePublished":68,"encodingFormat":66,"isAccessibleForFree":69,"interactionStatistic":70},"DigitalDocument",{"url":57,"@type":58,"width":59,"height":60},"https://docshare.wps.com/thumbnails/ox40l-and-il-2-combination-strategy-for-gastric-cancer-immunotherapy/448510.png","ImageObject",300,407,{"name":9,"@type":62},"Person",{"url":41,"name":64,"@type":65},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":71,"interactionType":72,"userInteractionCount":11},"InteractionCounter",{"@type":73},"ViewAction",{"@type":75,"mainEntity":76},"FAQPage",[77,83,87],{"name":78,"@type":79,"acceptedAnswer":80},"Why is combination therapy with IL-2 and OX40L considered for gastric cancer immunotherapy?","Question",{"text":81,"@type":82},"Because gastric cancer tumor microenvironments show inadequate T-cell activation and impaired costimulatory signaling, the study tests whether IL-2 and OX40L dual stimulation can synergistically enhance antitumor immunity.","Answer",{"name":84,"@type":79,"acceptedAnswer":85},"What experiments were used to assess IL-2 and OX40L effects?",{"text":86,"@type":82},"The study analyzes OX40/OX40L expression in gastric tissues and TILs, evaluates immunostimulatory effects of IL-2 and OX40L alone or together in PBMCs and TILs, and constructs a recombinant adenoviral vector co-expressing IL-2 and OX40L.",{"name":88,"@type":79,"acceptedAnswer":89},"What were the main findings from the IL-2/OX40L strategy?",{"text":90,"@type":82},"The IL-2 and OX40L combination significantly enhanced T-cell activation in both PBMCs and TILs and increased antitumor effector molecule expression. The adenoviral IL-2/OX40L vector effectively activated TILs, which then induced prominent apoptosis in primary gastric cancer tumor cells.","https://schema.org",{"og:url":52,"og:type":93,"og:title":13,"og:site_name":64,"og:description":14},"article",{"robots":95,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},1791250486,{"code":4,"msg":5,"data":99},[100,104,108,112,117,122,125,130,135,138,142],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":101,"show_sort_weight":102,"slug":103},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":105,"show_sort_weight":106,"slug":107},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":109,"show_sort_weight":110,"slug":111},"Exam",70,"exam",{"id":113,"doc_module":4,"doc_module_name":46,"category_name":114,"show_sort_weight":115,"slug":116},5,"Comic",60,"comic",{"id":118,"doc_module":4,"doc_module_name":46,"category_name":119,"show_sort_weight":120,"slug":121},6,"Technology",50,"technology",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":123,"slug":124},40,"healthcare",{"id":126,"doc_module":4,"doc_module_name":46,"category_name":127,"show_sort_weight":128,"slug":129},8,"Research & Report",30,"research-report",{"id":131,"doc_module":4,"doc_module_name":46,"category_name":132,"show_sort_weight":133,"slug":134},9,"Religion & Spirituality",20,"religion-spirituality",{"id":133,"doc_module":4,"doc_module_name":46,"category_name":136,"show_sort_weight":133,"slug":137},"World Cup","world-cup",{"id":139,"doc_module":4,"doc_module_name":46,"category_name":140,"show_sort_weight":139,"slug":141},10,"Lifestyle","lifestyle",{"id":143,"doc_module":4,"doc_module_name":46,"category_name":144,"show_sort_weight":113,"slug":145},19,"General","general"]