[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-384444-105":59,"doc-detail-384444-en":122},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":115,"head_meta":117,"extra_data":119,"updated_unix":121},105,"en","overcoming-cancer-associated-fibroblast-induced-immunosuppression-by-anti-interleukin-6-receptor-antibody","Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody","","Cancer-associated fibroblasts (CAFs) are a central component of the tumor microenvironment and strongly contribute to tumor progression through immunosuppression. The study investigates whether an anti-IL-6 receptor antibody can function as systemic therapy against cancer and clarifies how IL-6 drives immunosuppression. Clinical and mechanistic evidence links IL-6 with immunosuppressive phenotypes, including HIF1α-mediated glucose competition, and demonstrates that MR16-1 reverses CAF-induced immunosuppression and suppresses tumor progression, improving survival across cancers.",{"@graph":69,"@context":114},[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/overcoming-cancer-associated-fibroblast-induced-immunosuppression-by-anti-interleukin-6-receptor-antibody/384444/",{"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/overcoming-cancer-associated-fibroblast-induced-immunosuppression-by-anti-interleukin-6-receptor-antibody/384444.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"What effect does an anti-IL-6 receptor antibody have in experimental models?","Question",{"text":112,"@type":113},"The rodent analog MR16-1 overcomes CAF-induced immunosuppression and suppresses tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},384444,1790579585,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":131,"language":132,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":133,"faqs":134,"seo_title":135,"seo_description":67,"update_tm":136,"read_time":36},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Cancer Immunology, Immunotherapy (2023) 72:2029–2044  \n[https://doi.org/10.1007/s00262-023-03378-7](https://doi.org/10.1007/s00262-023-03378-7)  \nOvercoming cancer‑associated fibroblast‑induced  \nimmunosuppression by anti‑interleukin‑6 receptor antibody  \nNoriyuki Nishiwaki1 · Kazuhiro Noma1 · Toshiaki Ohara1,2 · Tomoyoshi Kunitomo1 · Kento Kawasaki1 · Masaaki Akai1 · Teruki Kobayashi1 · Toru Narusaka1 · Hajime Kashima1 · Hiroaki Sato1 · Satoshi Komoto1 · Takuya Kato1 · Naoaki Maeda1 · Satoru Kikuchi1 · Shunsuke Tanabe1 · Hiroshi Tazawa1,3 · Yasuhiro Shirakawa1,4 · Toshiyoshi Fujiwara1  \nReceived: 18 April 2022 / Accepted: 15 January 2023 / Published online: 10 February 2023 © The Author(s) 2023  \nAbstract  \nCancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a central role in tumor progression. Previously, we reported that CAFs might induce tumor immunosuppression via interleukin-6 (IL-6) and promote tumor progression by blocking local IL-6 in the tumor microenvironment with neutralizing antibody. Here, we explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, and further investigate the mechanisms by which IL-6 induces tumor immunosuppression. In clinical samples, IL-6 expression was significantly correlated with α-smooth muscle actin expression, and high IL-6 cases showed tumor immunosuppression. Multivariate analysis showed that IL-6 expression was an independent prognostic factor. In vitro, IL-6 contributed to cell proliferation and differentiation into CAFs. Moreover, IL-6 increased hypoxia-inducible factor 1α (HIF1α) expression and induced tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. MR16-1, a rodent analog of anti-IL-6 receptor antibody, overcame CAF-induced immunosuppression and suppressed tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo. The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation.  \nKeywords Cancer-associated fibroblasts · Drug repositioning · Interleukin-6 receptor antibody · Tumor microenvironment  \nAbbreviations  \nBMDM Bone marrow-derived monocytes  \nCAF Cancer-associated fibroblast  \nCI Confidence interval  \nCOVID-19 Coronavirus Disease 2019  \n* Kazuhiro Noma[knoma@md.okayama-u.ac.jp](knoma@md.okayama-u.ac.jp)  \n1 Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Kita-ku, Okayama 700-8558, Japan  \n2 Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan  \n3 Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan  \n4 Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan  \nCTL  \nDFS  \nEC  \nEMR  \nESD  \nFoxP3  \nGLUT  \nHIF1α  \nHR  \nIba1  \nIF  \nIHC  \nIL  \nIL-6Rα  \nJCRB  \nMDSC  \nM-CSF  \nCytotoxic T-cells  \nDisease-free survival Esophageal cancer Endoscopic mucosal resection  \nEndoscopic submucosal dissection Forkhead box protein 3  \nGlucose transporter Hypoxia-inducible factor 1α Hazard ratio  \nIonized calcium-binding adaptor protein 1 Immunofluorescence Immunohistochemistry  \nInterleukin  \nInterleukin-6 receptor alpha Japanese Collection of Research Bioresources  \nMyeloid-derived suppressor cell Mouse macrophage colony-stimulating factor  \nOS Overall survival  \nPI3K Phosphatidylinositol-3 kinase  \nPMA Phorbol-12-myristate-13-acetate  \nRT Room temperature  \nSE Standard error  \nSMA Smooth muscle actin  \nSTAT Signal transducer and activator of  \ntranscription  \nTAM Tumor-associated macrophage  \nTCZ Tocilizumab  \nTIL Tumor-infiltrating lymphocyte  \nTME Tumor microenv","cbCaibc5ahdsaAxX","https://ap.wps.com/l/cbCaibc5ahdsaAxX","pdf",6180225,16,"English","# Abstract\n# Keywords\n# Abbreviations\n# Introduction","[{\"question\":\"What effect does an anti-IL-6 receptor antibody have in experimental models?\",\"answer\":\"The rodent analog MR16-1 overcomes CAF-induced immunosuppression and suppresses tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo.\"}]","Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody | PDF",1790263304]