[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-356269-105":59,"doc-detail-356269-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","the-tumor-microenvironment-adding-pieces-to-the-puzzle","The tumor microenvironment: adding pieces to the puzzle","","The review analyzes how the tumor microenvironment (TME) functions as a dynamic, heterogeneous ecosystem where malignant cells continuously interact with stromal, immune, endothelial cells, and extracellular matrix proteins. It integrates evidence on intercellular networks that shape immune defense while paradoxically enabling tumor progression and therapeutic resistance. The synthesis highlights immune-cell and stromal contributions, emphasizing homeostatic processes, metabolic reprogramming, oxidative stress, and extracellular vesicle–mediated signaling as drivers of pro-tumor communication and resistance.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-tumor-microenvironment-adding-pieces-to-the-puzzle/356269/",{"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/the-tumor-microenvironment-adding-pieces-to-the-puzzle/356269.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What does the tumor microenvironment (TME) involve?","Question",{"text":113,"@type":114},"The TME consists of malignant cells interacting directly or indirectly with stromal, immune, endothelial cells, and extracellular matrix proteins. These interactions occur through membrane contact and soluble factors, and the composition changes during tumor development.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does the TME influence the immune response?",{"text":118,"@type":114},"The TME can modulate immunity in a dual way: some immune subsets retain cytotoxic functions, while others become regulatory or exhausted, suppressing anti-tumor immunity and facilitating tumor growth.",{"name":120,"@type":111,"acceptedAnswer":121},"Which mechanisms are highlighted as contributors to tumor resistance?",{"text":122,"@type":114},"The review emphasizes metabolic reprogramming and oxidative stress, along with extracellular vesicle–mediated signaling, as factors that confer tumor resistance and enable pro-tumor communication networks.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},356269,1790136538,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","TYPE Review  \nPUBLISHED 12 January 2026  \nDOI 10.3389/fimmu.2025.1731338  \nOPEN ACCESS  \nEDITED BY  \nSudarshan Kini,  \nNitte (Deemed to be University), India  \nREVIEWED BY  \nBhupendra Gopalbhai Prajapati, Parul University, India  \nChi-Heng Wu,  \nDren Bio, Inc., United States  \n*CORRESPONDENCE  \nJose S. Lopez-Gonzalez  \n [slopezgonzalez@yahoo.com](slopezgonzalez@yahoo.com);  \n [sullivan.lopez@iner.gob. mx](sullivan.lopez@iner.gob. mx)[ ](sullivan.lopez@iner.gob. mx)†These authors share first authorship  \nRECEIVED 24 October 2025  \nREVISED 11 December 2025  \nACCEPTED 17 December 2025  \nPUBLISHED 12 January 2026  \nCITATION  \nAguilar-Cazares D, Perez-Medina M, Benito-Lopez JJ, Galicia-Velasco M, Meneses-Flores M, Camarena A and Lopez-Gonzalez JS (2026) The tumor  \nmicroenvironment: adding pieces to the puzzle.  \nFront. Immunol. 16:1731338 .  \ndoi: 10.3389/fimmu.2025.1731338  \nCOPYRIGHT  \n© 2026 Aguilar-Cazares, Perez-Medina, Benito-Lopez, Galicia-Velasco, Meneses-Flores, Camarena and Lopez-Gonzalez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The 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.  \nThe tumor microenvironment: adding pieces to the puzzle  \nDolores Aguilar-Cazares 1†, Mario Perez-Medina 1,2†, Jesus J. Benito-Lopez 1, Miriam Galicia-Velasco 1, Manuel Meneses-Flores 1, Angel Camarena 3 and Jose S. Lopez-Gonzalez 1*  \n1 Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades CronicoDegenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, Mexico, 2 Department of Research, Asociación Para Evitar la Ceguera en México IAP, Mexico City, Mexico, 3 Laboratorio de Inmunobiologia y Genetica, Instituto Nacional de Enfermedades Respiratorias “Ismael Coso Villegas”, Mexico City, Mexico  \nIn the tumor microenvironment, malignant cells coexist and interact with eachother and with stromal, immune, and endothelial cells, as well as with extracellular matrix proteins. The interaction occurs through membrane contact or the production of multiple soluble factors. The composition of tumor and matrix cells changes continuously during tumor development, along with the infiltration of immune cells, forming heterogeneous niches that vary in space and time. We integrate current knowledge about the complex interaction between heterogeneous cell populations in the TME and the impact of these networks in supporting immune defense, which paradoxically promotes tumor progression. We summarize the involvement of immune cells and highlight the impact of certain homeostatic processes mediated by stromal cell populations and matrix components on tumor development. We propose the role of metabolic reprogramming and oxidative stress, as well as extracellular vesicle-mediated signaling, in conferring tumor resistance and therapeutic strategies to disrupt pro-tumor communication networks while enhancing anti-tumor immunity. Our goal is to provide a comprehensive framework for understanding and addressing the cellular interactions underlying cancer progression, fostering opportunities to formulate strategies that control tumor growth and eliminate resistance to treatment options. This integrative perspective provides a basis for designing multi-targeted immunotherapies aimed at rewiring pro-tumor communication networks.  \nKEYWORDS  \nextracellular vesicles, immune checkpoints, immune response, metabolic reprograming, resistance, stroma cells, tissue remodeling, tumor evasion mechanisms  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nThe tumor microenvironment (TME) is a dynamic and heterogeneous ecosystem in which m","cbCaiiftb4rPzCfx","https://ap.wps.com/l/cbCaiiftb4rPzCfx","pdf",2645820,22,"English","# Introduction\n## Tumor microenvironment as a dynamic system\n## High-dimensional profiling and cell-cell communication\n## Immune modulation and pro-tumor shifts","[{\"question\":\"What does the tumor microenvironment (TME) involve?\",\"answer\":\"The TME consists of malignant cells interacting directly or indirectly with stromal, immune, endothelial cells, and extracellular matrix proteins. These interactions occur through membrane contact and soluble factors, and the composition changes during tumor development.\"},{\"question\":\"How does the TME influence the immune response?\",\"answer\":\"The TME can modulate immunity in a dual way: some immune subsets retain cytotoxic functions, while others become regulatory or exhausted, suppressing anti-tumor immunity and facilitating tumor growth.\"},{\"question\":\"Which mechanisms are highlighted as contributors to tumor resistance?\",\"answer\":\"The review emphasizes metabolic reprogramming and oxidative stress, along with extracellular vesicle–mediated signaling, as factors that confer tumor resistance and enable pro-tumor communication networks.\"}]","The tumor microenvironment: adding pieces to the puzzle | PDF",1790124357,55]