[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-368838-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-368838-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","multimodal-therapeutic-strategies-against-gastric-cancer-from-conventional-treatments-to-tumor-microenvironment-targeting","Multimodal therapeutic strategies against gastric cancer - from conventional treatments to tumor microenvironment targeting","","Review article examining how tumor immune microenvironment (TIME) heterogeneity shapes treatment response and prognosis in gastric cancer. It highlights cellular heterogeneity and metabolic reprogramming as key mechanisms that remodel the immune landscape and drive immune evasion. Summarizes traditional treatment modalities and consolidates existing and potential strategies designed to modulate the microenvironment. Focuses on how targeting cellular components, molecular profiles, metabolism, and spatial tumor-immune interactions may improve outcomes.",{"@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/multimodal-therapeutic-strategies-against-gastric-cancer-from-conventional-treatments-to-tumor-microenvironment-targeting/368838/",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/multimodal-therapeutic-strategies-against-gastric-cancer-from-conventional-treatments-to-tumor-microenvironment-targeting/368838.png","ImageObject",300,407,{"name":42,"@type":43},"4398046744996","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is TIME considered a major barrier to conventional gastric cancer therapies?","Question",{"text":63,"@type":64},"The immunosuppressive tumor immune microenvironment constrains treatment effectiveness and is strongly associated with prognosis. Its dynamic heterogeneity can limit therapeutic benefit and enable immune evasion.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What forms of heterogeneity within TIME are discussed as influencing prognosis and therapy response?",{"text":68,"@type":64},"TIME heterogeneity includes differences in immune cells, extracellular matrix, soluble factors (e.g., cytokines and chemokines), metabolites, and the spatial distribution of tumor cells.",{"name":70,"@type":61,"acceptedAnswer":71},"Which microenvironment-related treatment strategies are highlighted as emerging options?",{"text":72,"@type":64},"The review emphasizes precise modulation of the tumor microenvironment, including targeted therapies that exploit tumor-specific markers and immunotherapies that reverse tumor-induced immune inhibition.","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},368838,1790217107,{"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":11,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"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},4398046744996,"TYPE Review  \nPUBLISHED 04 September 2025 DOI 10.3389/fimmu.2025.1623588  \nOPEN ACCESS  \nEDITED BY  \nMatteo Fassan,  \nUniversity of Padua, Italy  \nREVIEWED BY  \nThomas Böldicke,  \nHelmholtz Association of German Research Centers (HZ), Germany  \nGaurav Kandoi,  \nInvaio Sciences, United States  \n*CORRESPONDENCE  \nChunming Li  \n [naliang@zmu.edu.cn](naliang@zmu.edu.cn)  \nRECEIVED 06 May 2025  \nACCEPTED 25 August 2025  \nPUBLISHED 04 September 2025  \nCITATION  \nYuan X, Chen C, Pang Y, Wang X, Yang T, Long A, Liang N, Yang Y and Li C (2025) Multimodal therapeutic strategies against gastric cancer: from conventional treatments to tumor microenvironment targeting.  \nFront. Immunol. 16:1623588 .  \ndoi: 10.3389/fimmu.2025.1623588  \nCOPYRIGHT  \n© 2025 Yuan, Chen, Pang, Wang, Yang, Long, Liang, Yang and Li. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nMultimodal therapeutic strategies against gastric cancer: from conventional treatments to tumor microenvironment targeting  \nXi Yuan 1,2, Changxian Chen 1,2, Yixuan Pang 1,2, Xuanzhi Wang 3, Tingting Yang 1,2, Anying Long 1,2, Na Liang 1,2, Ying Yang 1,2 and Chunming Li 1,2*  \n1 Department of Pathology, Zunyi Medical University, Zunyi, Guizhou, China, 2 Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China, 3The First Clinical Institute, Zunyi Medical University, Zunyi, Guizhou, China  \nGastric cancer is one of the most common malignant tumors of the digestive system, with persistently high global morbidity and mortality rates. The multilevel heterogeneity of the gastric cancer tumor immune microenvironment (TIME) is closely associated with treatment efficacy and prognosis. This heterogeneity is reflected not only in the types and functions of various cells within the microenvironment but also in multiple aspects such as molecular profiles, metabolic pathways, and the spatial distribution of tumor cells. Currently, the interaction between gastric cancer and its microenvironment, as well as the resulting immune evasion, has become a research hotspot. This article reviews the role of cellular heterogeneity and metabolic reprogramming in the gastric cancer Tumor Immune Microenvironment (TIME) in reshaping the immune microenvironment, and summarizes traditional therapies alongside existing and potential microenvironment-modulating treatment strategies.  \nKEYWORDS  \ngastric cancer, tumor immune microenvironment, heterogeneity of cell components, metabolic reprogramming, immunotherapy  \n1 Introduction  \nGastric cancer is a common malignant tumor of the digestive system, with morbidity and mortality rates ranking among the highest worldwide (1) . Due to its high invasiveness, susceptibility to metastasis, and drug resistance, traditional treatment methods face significant challenges. Surgical resection combined with adjuvant chemotherapy or chemoradiotherapy remains the cornerstone of treatment. While surgery swiftly eradicates localized disease, it is inadequate against systemic micrometastases. Chemotherapy, with its systemic reach, is backed by robust evidence and extensive  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nclinical experience; however, its efficacy is tempered by significant toxicity and tumor heterogeneity, limiting overall benefit. Radiotherapy can effectively reduce tumor burden, yet it often harms surrounding healthy tissues and carries a risk of treatmentrelated complications (2–6) . Systemic antineoplastic therapy remains the cornerstone for advanced, unresectable, or metastatic gastric cancer (4) . The effectiveness of ","cbCaie84BTGWmvD7","https://ap.wps.com/l/cbCaie84BTGWmvD7","pdf",5071016,17,"English","# Introduction\n## Tumor immune microenvironment (TIME) heterogeneity and treatment barriers\n## Conventional therapies and their limitations\n## Rationale for microenvironment-modulating strategies\n# Emerging targeted and immunotherapeutic approaches","[{\"question\":\"Why is TIME considered a major barrier to conventional gastric cancer therapies?\",\"answer\":\"The immunosuppressive tumor immune microenvironment constrains treatment effectiveness and is strongly associated with prognosis. Its dynamic heterogeneity can limit therapeutic benefit and enable immune evasion.\"},{\"question\":\"What forms of heterogeneity within TIME are discussed as influencing prognosis and therapy response?\",\"answer\":\"TIME heterogeneity includes differences in immune cells, extracellular matrix, soluble factors (e.g., cytokines and chemokines), metabolites, and the spatial distribution of tumor cells.\"},{\"question\":\"Which microenvironment-related treatment strategies are highlighted as emerging options?\",\"answer\":\"The review emphasizes precise modulation of the tumor microenvironment, including targeted therapies that exploit tumor-specific markers and immunotherapies that reverse tumor-induced immune inhibition.\"}]","Multimodal therapeutic strategies against gastric cancer - from conventional treatments to tumor microenvironment targeting | PDF",1790178895,43]