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Mechanistically, RAB10 delivered by breast cancer cells binds IFNAR1 and suppresses JAK1/STAT1 phosphorylation, blocking M1 polarization while promoting M2 polarization. Elevated RAB10 in drug-resistant cells correlates with poor prognosis. In vitro and in vivo experiments show reduced proliferation, invasion, and epithelial–mesenchymal transition after RAB10 knockdown. Single-cell RNA sequencing indicates fewer macrophages in the TME, with increased immunosuppressive signaling and diminished CD8+ T-cell activity. Combined RAB10 and PD-L1 targeting synergistically inhibits tumor growth, supporting exosomal RAB10 as a therapeutic strategy.",{"@graph":14,"@context":76},[15,34,55],{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/exosome-rab10-inhibits-jak1stat1-to-hinder-macrophage-m1-polarization-and-promote-tumor-immune-escape-research-open-access/358710/",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/exosome-rab10-inhibits-jak1stat1-to-hinder-macrophage-m1-polarization-and-promote-tumor-immune-escape-research-open-access/358710.png","ImageObject",300,407,{"name":42,"@type":43},"Oliver","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-24","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68,72],{"name":59,"@type":60,"acceptedAnswer":61},"How does exosomal RAB10 affect macrophage polarization in this study?","Question",{"text":62,"@type":63},"Exosomal RAB10 binds to IFNAR1 and inhibits phosphorylation of the JAK1/STAT1 pathway, thereby blocking macrophage M1 polarization while promoting an M2 polarization shift.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What evidence links RAB10 to breast cancer drug resistance and patient outcomes?",{"text":67,"@type":63},"RAB10 expression is significantly upregulated in drug-resistant breast cancer cells and correlates with poor patient prognosis, supporting its association with therapeutic resistance.",{"name":69,"@type":60,"acceptedAnswer":70},"What is the impact of RAB10 knockdown on tumor growth and tumor-associated markers?",{"text":71,"@type":63},"In vivo RAB10 knockdown suppresses tumor growth and reduces markers related to proliferation (Ki67, PCNA), invasion (MMP2), and epithelial–mesenchymal transition (Snail, Vimentin).",{"name":73,"@type":60,"acceptedAnswer":74},"Why might combining RAB10 targeting with PD-L1 blockade be effective?",{"text":75,"@type":63},"The study shows that RAB10 inhibition shifts macrophage phenotypes toward reduced immunogenic activity and increases immunosuppressive signaling; PD-L1 blockade alongside RAB10 targeting produces a synergistic inhibitory effect on tumor growth.","https://schema.org",{"og:url":32,"og:type":78,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":80,"canonical":32},"index,follow",{"doc_id":82,"site_id":7},358710,1790209684,{"code":4,"msg":85,"data":86},"success",[87,91,95,99,104,109,114,118,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},"Exam",70,"exam",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},5,"Comic",60,"comic",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},6,"Technology",50,"technology",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},7,"Healthcare",40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":116,"slug":117},8,30,"research-report",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},9,"Religion & Spirituality",20,"religion-spirituality",{"id":121,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":121,"slug":125},"World Cup","world-cup",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":127,"slug":129},10,"Lifestyle","lifestyle",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":100,"slug":133},19,"General","general",{"code":4,"msg":85,"data":135},{"doc_id":82,"user_id":136,"nickname":42,"user_avatar":137,"doc_module":4,"category_id":115,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":143,"language":144,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":12,"update_tm":148,"read_time":149},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Guohui et al. Cell Communication and Signaling (2026) 24:123  \n[https://doi.org/10.1186/s12964-026-02681-x](https://doi.org/10.1186/s12964-026-02681-x)  \nCell Communication and Signaling  \nRESEARCH Open Access  \nExosome RAB10 inhibits JAK1/STAT1 to hinder   macrophage M1 polarization and promote tumor immune escape  \nTang Guohui1,2†, Pang Bo1,2†, Yuting Liu1†, Shaopeng Xu5, Li Ruonan1, Zhu Chengle1, Wu Qiong1, Ran Ruorong1,2, Haotian Cai1, Wang Wenrui1,2,3*, Chen Changjie1,3* and Yang Qingling1,3,4*  \nAbstract  \nExosomes are key mediators of communication between tumor cells and the tumor microenvironment(TME); however, the mechanisms underlying exosome-mediated crosstalk between tumor cells and macrophages remain largely unclear. This study investigated the effect of exosomal RAB10 on macrophage polarization and tumor growth. Mechanistically, RAB10 delivered by breast cancer cells binds to the interferon receptor IFNAR1 and inhibits JAK1/STAT1 pathway phosphorylation, thereby impeding M1 polarization and promoting M2 polarization. RAB10 expression was significantly upregulated in drug-resistant breast cancer cells and was correlated with poor patient prognosis. In vitro assays confirmed that RAB10 enhances cancer cell proliferation. In vivo knockdown of RAB10 suppressed tumor growth and reduced the expression of markers related to proliferation (Ki67, PCNA), invasion (MMP2), and epithelial–mesenchymal transition (Snail, Vimentin) . Single-cell RNA sequencing revealed a marked decrease in the proportion of macrophages in the TME following RAB10 knockdown. This phenotypic shift increases the secretion of immunosuppressive factors such as PDL1, leading to reduced activity of CD8⁺ T cells. Animal studies further confirmed that combined targeting of RAB10 and PD-L1 produces a synergistic inhibitory effect on tumor growth. This study demonstrated that breast cancer cells can transfer RAB10 to macrophages via exosomes. RAB10 interacts with IFNAR1 to suppress the JAK1/STAT1 signaling pathway, thereby inhibiting M1 polarization and promoting M2 polarization of macrophages. Inhibition of RAB10, especially in combination with PD-L1 blockade, offers a promising strategy to enhance anti-tumor immunity and overcome therapeutic resistance in breast cancer.  \nKeywords RAB10, Breast cancer, Exosomes, Macrophage polarization, scRNA-seq  \n†Tang Guohui, Pang Bo andYuting Liu co-first author.  \n*Correspondence:  \nWangWenrui [wenrui-wang1983@163.com](wenrui-wang1983@163.com)[ ](wenrui-wang1983@163.com)Chen Changjie [tochenchangjie@163.com](tochenchangjie@163.com)[ ](tochenchangjie@163.com)Yang Qingling [yqlmimi@163.com](yqlmimi@163.com)  \n1Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Anhui  \n233030, China  \n2Department of Life Sciences, Bengbu Medical University, Anhui 233030, China  \n3Department of Biochemistry and Molecular Biology, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui 233030, China 4Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui, China  \n5The third the People’s Hospital of Bengbu, Anhui 233030, China  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is","cbCaiuiJmXq6AIFB","https://ap.wps.com/l/cbCaiuiJmXq6AIFB","pdf",10608843,18,"English","# Abstract\n# Background","[{\"question\":\"How does exosomal RAB10 affect macrophage polarization in this study?\",\"answer\":\"Exosomal RAB10 binds to IFNAR1 and inhibits phosphorylation of the JAK1/STAT1 pathway, thereby blocking macrophage M1 polarization while promoting an M2 polarization shift.\"},{\"question\":\"What evidence links RAB10 to breast cancer drug resistance and patient outcomes?\",\"answer\":\"RAB10 expression is significantly upregulated in drug-resistant breast cancer cells and correlates with poor patient prognosis, supporting its association with therapeutic resistance.\"},{\"question\":\"What is the impact of RAB10 knockdown on tumor growth and tumor-associated markers?\",\"answer\":\"In vivo RAB10 knockdown suppresses tumor growth and reduces markers related to proliferation (Ki67, PCNA), invasion (MMP2), and epithelial–mesenchymal transition (Snail, Vimentin).\"},{\"question\":\"Why might combining RAB10 targeting with PD-L1 blockade be effective?\",\"answer\":\"The study shows that RAB10 inhibition shifts macrophage phenotypes toward reduced immunogenic activity and increases immunosuppressive signaling; PD-L1 blockade alongside RAB10 targeting produces a synergistic inhibitory effect on tumor growth.\"}]","Exosome RAB10 inhibits JAK1/STAT1 to hinder macrophage M1 polarization and promote tumor immune escape - Research Open Access | PDF",1790135040,45]