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Distinct resident immune and stromal cell types, including CAFs, TAMs, neutrophils, and NK cells, shape metastasis and immune interactions and sustain TME heterogeneity. Tumor-cell-derived extracellular vesicles (EVs) transfer RNA, proteins, peptides, and lipids, converting normal cells into tumor-associated protumorigenic counterparts, while supporting cancer diagnosis and therapy; the review emphasizes exosome-mediated transformations and their functional roles.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/tumor-microenvironment-modulation-by-cancer-derived-extracellular-vesicles/332016/",{"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/tumor-microenvironment-modulation-by-cancer-derived-extracellular-vesicles/332016.png","ImageObject",300,407,{"name":92,"@type":93},"Ava Thompson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",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 role does the tumor microenvironment (TME) play in cancer development?","Question",{"text":113,"@type":114},"The TME regulates tumor-cell growth, metabolism, proliferation, invasion, and contributes to resistance to conventional chemoradiotherapies. 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Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles. Cells 2024, 13, 682. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13080682  \nAcademic Editors: Silvia Peppicelli and Kiyotaka Shiba  \nReceived: 11 February 2024  \nRevised: 6 April 2024  \nAccepted: 11 April 2024  \nPublished: 15 April 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 School of Medicine and Life Sciences, Far Eastern Federal University, 690922 Vladivostok, Russia; [ten.arteym@gmail.com](ten.arteym@gmail.com) (A.T.); [frear.far@mail.ru](frear.far@mail.ru) (V.K.); [vkumeiko@yandex.ru](vkumeiko@yandex.ru) (V.F.)  \n2 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; [gaohuile@scu.edu.cn](gaohuile@scu.edu.cn)  \n3 Laboratory of Biomedical Nanotechnologies, Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave., 4, 194064 St. Petersburg, Russia  \n4 Personalized Medicine Centre, Almazov National Medical Research Centre, Akkuratova Str., 2,  \n197341 St. Petersburg, Russia  \n5 Department of Radiation Oncology, Technishe Universität München (TUM), Klinikum Rechts der Isar, Ismaninger Str., 22, 81675 Munich, Germany  \n* Correspondence: maxim.shevtsov@tum.de; Tel.: +49-173-1488882  \nAbstract: The tumor microenvironment (TME) plays an important role in the process of tumorigenesis, regulating the growth, metabolism, proliferation, and invasion of cancer cells, as well as contributing to tumor resistance to the conventional chemoradiotherapies. Several types of cells with relatively stable phenotypes have been identified within the TME, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils, and natural killer (NK) cells, which have been shown to modulate cancer cell proliferation, metastasis, and interaction with the immune system, thus promoting tumor heterogeneity. Growing evidence suggests that tumor-cell-derived extracellular vesicles (EVs), via the transfer of various molecules (e.g., RNA, proteins, peptides, and lipids), play a pivotal role in the transformation of normal cells in the TME into their tumor-associated protumorigenic counterparts. This review article focuses on the functions of EVs in the modulation of the TME with a view to how exosomes contribute to the transformation of normal cells, as well as their importance for cancer diagnosis and therapy.  \nKeywords: tumor microenvironment; exosome; cancer stem cell; cancer-associated fibroblast; tumorassociated macrophage; cancer-associated neutrophil; cancer-associated endothelial cells  \n1. Introduction  \nExtracellular vesicles (EVs) are lipid-membrane-bound secretory structures that play a crucial role in cancer biology, mediating intercellular communication between tumor and normal cells within the tumor microenvironment (TME) [1] . According to the International Society for Extracellular Vesicles (and MISEV2024 update), EVs are classified according to various criteria, as follows: (a) biogenesis pathway—endosome-origin “exosomes” or plasma-membrane-derived “ectosomes”(i.e., microparticles/microvesicles); (b) size—small (\u003C100 nm) or large (>200 nm); (c) biochemical composition (CD63+/CD81+-EVs, a","cbCaitS0oMwFDr7D","https://ap.wps.com/l/cbCaitS0oMwFDr7D","pdf",4440190,"English","# Abstract\n# Keywords\n# 1. Introduction\n## EV classification and biogenesis pathways","[{\"question\":\"What role does the tumor microenvironment (TME) play in cancer development?\",\"answer\":\"The TME regulates tumor-cell growth, metabolism, proliferation, invasion, and contributes to resistance to conventional chemoradiotherapies. It also supports tumor heterogeneity through interactions among multiple cell types.\"},{\"question\":\"How are extracellular vesicles (EVs) classified in this review?\",\"answer\":\"EVs are classified by biogenesis pathway (exosomes vs ectosomes), size (small vs large), biochemical composition, and origin or physiological process. The review also describes a common pathway-based grouping including exomeres, exosomes, ectosomes, migrasomes, apoptotic bodies, and oncosomes.\"},{\"question\":\"What contents of EVs are highlighted as important for modulating the TME?\",\"answer\":\"Exosome contents include RNAs such as miRNA, lncRNA, and circRNA, DNA fragments, transcription factors, and signaling proteins. These cargos can influence recipient cells and promote tumor-associated phenotypes.\"}]","Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles | PDF",1789996314,76]