[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-382689-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-382689-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","g-mdsc-derived-exosomes-mediate-the-differentiation-of-m-mdsc-into-m2-macrophages-promoting-colitis-to-cancer-transition","G-MDSC-derived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition","","Granulocytic myeloid-derived suppressor cells (G-MDSCs) and their exosomes shape how monocytic MDSCs (M-MDSCs) differentiate into M2 macrophages, thereby driving colitis-associated cancer progression. The study investigates cross-talk and underlying mechanisms using immunofluorescence, FACS, immunoblotting, siRNA, and antibodies, including IL-6 antibody treatment and STAT3 inhibition in dextran sulfate sodium-induced colitis-to-cancer mice. Results show IL-6–mediated enrichment of exosomal miR-93–5p downregulates STAT3 activity, enhancing anti-STAT3 effects. Overall, combining STAT3 inhibition with strategies blocking IL-6–driven miR-93–5p production supports CAC prevention and treatment.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/g-mdsc-derived-exosomes-mediate-the-differentiation-of-m-mdsc-into-m2-macrophages-promoting-colitis-to-cancer-transition/382689/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/g-mdsc-derived-exosomes-mediate-the-differentiation-of-m-mdsc-into-m2-macrophages-promoting-colitis-to-cancer-transition/382689.png","ImageObject",300,407,{"name":42,"@type":43},"Angel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What cellular transition is investigated in this study?","Question",{"text":63,"@type":64},"The study examines how G-MDSC-derived exosomes promote the differentiation of M-MDSCs into M2 macrophages during colitis-to-cancer transition.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which molecular pathway links IL-6 to the exosomal miRNA mechanism?",{"text":68,"@type":64},"Chronic inflammation-driven IL-6 promotes synthesis of miR-93–5p in G-MDSCs via the IL-6R/JAK/STAT3 pathway, leading to miR-93–5p enrichment in G-MDSC exosomes.",{"name":70,"@type":61,"acceptedAnswer":71},"How do IL-6 blockade and STAT3 inhibition interact for CAC?",{"text":72,"@type":64},"Early use of IL-6 antibodies enhances the effect of STAT3 inhibitor against colitis-associated cancer.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},382689,1790293761,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},687207412472,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Open access Original research  \n G-MDSC-derived exosomes mediate the  \ndifferentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition  \nYungang Wang  ,1 Hongli Liu,2 Zhe Zhang,1 Dezhi Bian,1 Keke Shao,1 Shengjun Wang,3 Yanxia Ding  1  \nTo cite: Wang Y, Liu H, Zhang Z, et al. G-MDSCderived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition. Journal for ImmunoTherapy of Cancer 2023;11:e006166 . doi:10.1136/jitc-2022-006166  \n► Additional supplemental material is published online only. To view, please visit the journal online ([http://dx.doi.org/10](http://dx.doi.org/10) . 1136/jitc-2022-006166) .  \nYW and HL contributed equally. Accepted 25 January 2023  \n© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nYanxia Ding;  \n[wzidyx2010@163.com](wzidyx2010@163.com)  \nYungang Wang; [wyg1223@126.com](wyg1223@126.com)  \nDr Shengjun Wang; [sjwjs@ujs.edu.cn](sjwjs@ujs.edu.cn)  \nABSTRACT  \nBackgrounds In inflammatory bowel disease microenvironment, transdifferentiation of myeloidderived suppressor cells (MDSCs) and M2 macrophage accumulation are crucial for the transition of colitis-tocancer. New insights into the cross-talk and the underling mechanism between MDSCs and M2 macrophage during colitis-to-cancer transition are opening new avenues for colitis-associated cancer (CAC) prevention and treatment. Methods The role and underlying mechanism that granulocytic MDSCs (G-MDSCs) or exosomes (Exo) regulates the differentiation of monocytic MDSCs (M-MDSCs) into M2 macrophages were investigated using immunofluorescence, FACS, IB analysis, etc, and employing siRNA and antibodies. In vivo efficacy and mechanistic studies were conducted with dextran sulfate sodium-induced CAC mice, employed IL-6 Abs and STAT3 inhibitor.  \nResults G-MDSCs promote the differentiation of  \nM-MDSC into M2 macrophages through exosomal miR-93–5 p which downregulating STAT3 activity in MMDSC. IL-6 is responsible for miR-93–5 p enrichment in G-MDSC exosomes (GM-Exo) . Mechanistically, chronic inflammation-driven IL-6 promote the synthesis of miR- 93–5 p in G-MDSC via IL-6R/JAK/STAT3 pathway. Early use of IL-6 Abs enhances the effect of STAT3 inhibitor against CAC.  \nConclusions IL-6-driven secretion of G-MDSC exosomal miR-93–5 p promotes the differentiation of M-MDSC into M2 macrophages and involves a STAT3 signaling mechanism that promote colitis-to-cancer transition. Combining STAT3 inhibitors with strategies that inhibit IL- 6-mediated G-MDSC exosomal miR-93–5 p production is beneficial for the prevention and treatment of CAC.  \nINTRODUCTION  \nColitis-associated cancer (CAC) does not display the adenoma-carcinoma sequence which is typical for sporadic colorectal cancer (CRC) . Chronic inflammation and the increased turnover of epithelial cells contribute to the development of low-grade and high-grade dysplasia, which may further transform into CAC.1–3 Inflammatory bowel  \nWHAT IS ALREADY KNOWN ON THIS TOPIC  \n\n| ⇒ Myeloid-derived suppressor cells (MDSCs) and M2 macrophages accumulate under inflammatory bowel disease and colitis-associated cancer (CAC) conditions, but the interaction between them, as well as the role in regulating the transition of colitis-tocancer are unclear.\u003Cbr>WHAT THIS STUDY ADDS |\n| --- |\n| ⇒ Here, we report that granulocytic MDSCs (G-MDSCs) promote the differentiation of monocytic MDSC (MMDSC) into M2 macrophages through releasing exosomal miR-93–5 p. IL-6 is responsible for miR- 93–5 p enrichment in G-MDSC exosomes.\u003Cbr>HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY |\n\n⇒ These findings are the first to demonstrate that GMDSCs promote the differentiation of M-MDSC into M2 macrophages, thereby facilitating colitis-tocancer transition. Blocking the crosstalk between MDSCs and M2 is beneficial for the preve","cbCaitOuvFCZpYJ6","https://ap.wps.com/l/cbCaitOuvFCZpYJ6","pdf",9467232,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n# What Is Already Known on This Topic\n# What This Study Adds\n# How This Study Might Affect Research, Practice or Policy","[{\"question\":\"What cellular transition is investigated in this study?\",\"answer\":\"The study examines how G-MDSC-derived exosomes promote the differentiation of M-MDSCs into M2 macrophages during colitis-to-cancer transition.\"},{\"question\":\"Which molecular pathway links IL-6 to the exosomal miRNA mechanism?\",\"answer\":\"Chronic inflammation-driven IL-6 promotes synthesis of miR-93–5p in G-MDSCs via the IL-6R/JAK/STAT3 pathway, leading to miR-93–5p enrichment in G-MDSC exosomes.\"},{\"question\":\"How do IL-6 blockade and STAT3 inhibition interact for CAC?\",\"answer\":\"Early use of IL-6 antibodies enhances the effect of STAT3 inhibitor against colitis-associated cancer.\"}]","G-MDSC-derived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition | PDF",1790251882,33]