[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-407031-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-407031-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","gut-microbiota-reshaping-the-pancreatic-cancer-immune-microenvironment-new-avenues-for-immunotherapy","Gut microbiota reshaping the pancreatic cancer immune microenvironment - new avenues for immunotherapy","","Pancreatic cancer remains one of the deadliest malignancies due to its highly immunosuppressive tumor microenvironment and limited effectiveness of conventional treatments. Growing evidence shows the gut microbiota as a key regulator of antitumor immunity by shaping T-cell activation, macrophage polarization, and dendritic cell function. Microbial communities and metabolites can either impair or enhance immune surveillance, affecting immune checkpoint inhibitor and CAR-T efficacy. Dietary modulation, probiotics, fecal microbiota transplantation, and metabolite supplementation may restore immune balance and improve outcomes, while microbiome profiling supports biomarker discovery for response prediction and immune-related adverse events. This review consolidates insights into microbiota–immune interactions, microbiome-targeted therapies, and precision immunotherapy opportunities guided by microbial modulation.",{"@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/gut-microbiota-reshaping-the-pancreatic-cancer-immune-microenvironment-new-avenues-for-immunotherapy/407031/",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/gut-microbiota-reshaping-the-pancreatic-cancer-immune-microenvironment-new-avenues-for-immunotherapy/407031.png","ImageObject",300,407,{"name":42,"@type":43},"hdkawk","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",15,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is pancreatic cancer particularly challenging to treat with immunotherapy?","Question",{"text":63,"@type":64},"Pancreatic ductal adenocarcinoma features a highly immunosuppressive tumor microenvironment with dense desmoplasia, regulatory immune infiltration, and reduced effector T cells, which dampens antitumor immunity and limits response to immune checkpoint blockade.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the gut microbiota influence the pancreatic cancer immune microenvironment?",{"text":68,"@type":64},"The gut microbiota modulates both innate and adaptive immune processes, including T-cell activation, macrophage polarization, dendritic cell function, and immune surveillance. Microbial metabolite signaling and metabolic regulation can either inhibit or enhance antitumor immunity, thereby affecting immunotherapy efficacy.",{"name":70,"@type":61,"acceptedAnswer":71},"What microbiome-targeted interventions does the review highlight for improving immunotherapy outcomes?",{"text":72,"@type":64},"The review discusses dietary modulation, probiotics, fecal microbiota transplantation, and microbial metabolite supplementation to help restore immune homeostasis and improve treatment outcomes. It also notes gut microbiome profiling as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events.","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},407031,1790796114,{"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":55,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},3985747859855,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Zheng et al. Molecular Cancer (2025) 24:313 [https://doi.org/10.1186/s12943-025-02513-5](https://doi.org/10.1186/s12943-025-02513-5)  \nMolecular Cancer  \nREVIEW Open Access  \nGut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy  \nShi-Hang Zheng 1†, Ke-Zhu Li2†, Ge Feng3†, Yu-Tong Wang3, Jia-Ning Wang4*, Shu-Qiang Li5* andYing-Dong Sun6*  \nAbstract  \nPancreatic cancer remains one of the deadliest malignancies, primarily due to its highly immunosuppressive tumor microenvironment (TME) and poor response to conventional therapies. Increasing evidence highlights the gut microbiota as a pivotal regulator of antitumor immunity, modulating T cell activation, macrophage polarization, and dendritic cell function. Microbial communities and their metabolites can either inhibit or enhance immune surveillance, thereby influencing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy. Approaches including dietary modulation, probiotics, fecal microbiota transplantation (FMT), and microbial metabolite supplementation show promise in restoring immune homeostasis and improving treatment outcomes. Additionally, gut microbiome profiling has emerged as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events. This review summarizes current insights into microbiota–immune interactions in pancreatic cancer, emphasizes microbiome-targeted therapeutic strategies, and explores future opportunities for precision immunotherapy guided by microbial modulation.  \nKeywords Pancreatic cancer, Gut microbiota, Tumor microenvironment, Immunotherapy, Probiotics, Biomarkers  \n†Shi-Hang Zheng, Ke-Zhu Li and Ge Feng contributed equally to this work.  \n*Correspondence:  \nJia-Ning Wang [wangjianing05@hotmail.com](wangjianing05@hotmail.com)[ ](wangjianing05@hotmail.com)Shu-Qiang Li[lishuqiang@cmu.edu.cn](lishuqiang@cmu.edu.cn)[ ](lishuqiang@cmu.edu.cn)Ying-Dong Sun[ydsun@cmu.edu.cn](ydsun@cmu.edu.cn)  \n1Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, China  \n2Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang 110001, China  \n3Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, China  \n4Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, China 5Department of Hepatobiliary & Organ Transplantation Surgery, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Shenyang 110022, China  \n6Department of Vascular Surgery, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Shenyang 110022, China  \nIntroduction  \nPancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest cancers, with the five-year survival remaining below 10% even after progress in surgical techniques, chemotherapy, and targeted treatments [1, 2]. In contrast to malignancies like melanoma and non-small cell lung cancer, PDAC responds poorly to immune checkpoint blockade, which is mainly attributed to its distinctively immunosuppressive tumor microenvironment (TME) [3, 4]. The PDAC TME is characterized by dense desmoplasia, regulatory immune cell infiltration, and a paucity of effector T cells, all of which collectively dampen effective antitumor immunity [5, 6]. Therefore, unraveling novel mechanisms that reshape the immune landscape of PDAC is critical to improve immunotherapy outcomes.  \nRecent studies emphasize that gut microbiota functions as an important external regulator, shaping systemic as  \n© The Author(s) 2025. 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 t","cbCain28NOoIMBUa","https://ap.wps.com/l/cbCain28NOoIMBUa","pdf",1651699,"English","# Introduction\n# Gut microbiota as an external regulator of pancreatic cancer immunity\n# Microbial mechanisms shaping the tumor microenvironment\n## Macrophage polarization and effector immune suppression\n## Effects of microbial dysbiosis and microbial ablation\n# Probiotics and commensal bacteria in antitumor immunity\n## Lactobacillus casei and Lactobacillus reuteri\n## Th17 responses and related pathways","[{\"question\":\"Why is pancreatic cancer particularly challenging to treat with immunotherapy?\",\"answer\":\"Pancreatic ductal adenocarcinoma features a highly immunosuppressive tumor microenvironment with dense desmoplasia, regulatory immune infiltration, and reduced effector T cells, which dampens antitumor immunity and limits response to immune checkpoint blockade.\"},{\"question\":\"How does the gut microbiota influence the pancreatic cancer immune microenvironment?\",\"answer\":\"The gut microbiota modulates both innate and adaptive immune processes, including T-cell activation, macrophage polarization, dendritic cell function, and immune surveillance. Microbial metabolite signaling and metabolic regulation can either inhibit or enhance antitumor immunity, thereby affecting immunotherapy efficacy.\"},{\"question\":\"What microbiome-targeted interventions does the review highlight for improving immunotherapy outcomes?\",\"answer\":\"The review discusses dietary modulation, probiotics, fecal microbiota transplantation, and microbial metabolite supplementation to help restore immune homeostasis and improve treatment outcomes. It also notes gut microbiome profiling as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events.\"}]","Gut microbiota reshaping the pancreatic cancer immune microenvironment - new avenues for immunotherapy | PDF",1790569620,38]