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Cancer-associated fibroblasts (CAFs) represent key stromal components with diverse cellular origins, identifiable by markers such as a-SMA and FAP and explored as potential therapeutic targets. This review synthesizes evidence on CAF-driven effects on angiogenesis, immune suppression, invasion, and metastasis. It also highlights single-cell transcriptomics for CAF heterogeneity, CAF–immune system interactions that shape immunosuppression, and therapeutic strategies including CAF-targeted approaches and combinations with immunotherapy.",{"@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/cancer-associated-fibroblasts-in-gastrointestinal-cancers-unveiling-their-dynamic-roles-in-the-tumor-microenvironment/377415/",{"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/cancer-associated-fibroblasts-in-gastrointestinal-cancers-unveiling-their-dynamic-roles-in-the-tumor-microenvironment/377415.png","ImageObject",300,407,{"name":92,"@type":93},"Blitz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role do cancer-associated fibroblasts (CAFs) play in gastrointestinal cancer?","Question",{"text":113,"@type":114},"CAFs modulate tumors through effects on extracellular matrix, blood vessels, the immune system, tumor metabolism, and drug resistance, and they contribute to processes such as invasion and metastasis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which CAF markers are mentioned for identifying cancer-associated fibroblasts?",{"text":118,"@type":114},"The text highlights markers such as a-SMA and FAP for labeling CAFs, and notes that specific markers may serve as therapeutic targets.",{"name":120,"@type":111,"acceptedAnswer":121},"How is single-cell analysis used in understanding CAFs?",{"text":122,"@type":114},"Single-cell transcriptomics is discussed as a way to characterize CAF heterogeneity and to study their interactions within the tumor microenvironment.","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},377415,1790465135,{"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},24464137899374,"https://us-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Review  \nCancer-Associated Fibroblasts in Gastrointestinal Cancers:  \nUnveiling Their Dynamic Roles in the Tumor Microenvironment  \nNoor N. Al-Bzour 1, Ayah N. Al-Bzour 1, Obada E. Ababneh 2, Moayad M. Al-Jezawi 2, Azhar Saeed 3 and Anwaar Saeed 1,4, *  \nCitation: Al-Bzour, N.N.; Al-Bzour, A.N.; Ababneh, O.E.; Al-Jezawi, M.M.; Saeed, A.; Saeed, A.  \nCancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment. Int. J. Mol. Sci. 2023, 24, 16505. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms242216505](10.3390/ijms242216505)  \nAcademic Editor: Marina  \nK. Ibragimova  \nReceived: 3 October 2023  \nRevised: 15 November 2023  \nAccepted: 17 November 2023  \nPublished: 19 November 2023  \nCopyright: © 2023 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 Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA; [nnalbzour211@med.just.edu.jo](nnalbzour211@med.just.edu.jo) (N.N.A.-B.); [analbzour20@med.just.edu.jo](analbzour20@med.just.edu.jo) (A.N.A.-B.)  \n2 Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; [oeababneh185@med.just.edu.jo](oeababneh185@med.just.edu.jo) (O.E.A.); [mmaljezawei19@med.just.edu.jo](mmaljezawei19@med.just.edu.jo) (M.M.A.-J.)  \n3 Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; [azsaeed29@gmail.com](azsaeed29@gmail.com)  \n4 UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA  \n* Correspondence: [saeeda3@upmc.edu](saeeda3@upmc.edu); Tel.: +1-412-623-2091  \nAbstract: Gastrointestinal cancers are highly aggressive malignancies with significant mortality rates. Recent research emphasizes the critical role of the tumor microenvironment (TME) in these cancers, which includes cancer-associated fibroblasts (CAFs), a key component of the TME that have diverse origins, including fibroblasts, mesenchymal stem cells, and endothelial cells. Several markers, such asa-SMA and FAP, have been identified to label CAFs, and some specific markers may serve as potential therapeutic targets. In this review article, we summarize the literature on the multifaceted role of CAFs in tumor progression, including their effects on angiogenesis, immune suppression, invasion, and metastasis. In addition, we highlight the use of single-cell transcriptomics to understand CAF heterogeneity and their interactions within the TME. Moreover, we discuss the dynamic interplay between CAFs and the immune system, which contributes to immunosuppression in the TME, and the potential for CAF-targeted therapies and combination approaches with immunotherapy to improve cancer treatment outcomes.  \nKeywords: cancer-associated fibroblasts; gastrointestinal malignancies; single-cell analysis; immune system  \n1. Introduction  \nGastrointestinal (GI) cancers, including esophageal, gastric, liver, pancreatic, and colorectal cancers, constitute a group of highly aggressive malignancies with significant cancer-related mortalities [1] . In recent years, research has unveiled the pivotal role of the tumor microenvironment (TME) in the initiation and progression of these cancers. The TME is a complex network of non-cancerous host cells, such as fibroblasts, endothelial cells, neurons, adipocytes, adaptive and innate immune cells, as well as non-cellular components like the extracellular matrix (ECM), and various soluble products, including chemokines, cytokines, growth factors, and extracellular vesicles [2] .  \nAmong the diverse stromal cells within the TME, cancer-associated fibroblasts (CAFs) have emerged as they resemble the main co","cbCais3ZKZfnVB6f","https://ap.wps.com/l/cbCais3ZKZfnVB6f","pdf",756201,15,"English","# Abstract\n# 1. Introduction\n# 2. The Origin of Cancer-Associated Fibroblasts","[{\"question\":\"What role do cancer-associated fibroblasts (CAFs) play in gastrointestinal cancer?\",\"answer\":\"CAFs modulate tumors through effects on extracellular matrix, blood vessels, the immune system, tumor metabolism, and drug resistance, and they contribute to processes such as invasion and metastasis.\"},{\"question\":\"Which CAF markers are mentioned for identifying cancer-associated fibroblasts?\",\"answer\":\"The text highlights markers such as a-SMA and FAP for labeling CAFs, and notes that specific markers may serve as therapeutic targets.\"},{\"question\":\"How is single-cell analysis used in understanding CAFs?\",\"answer\":\"Single-cell transcriptomics is discussed as a way to characterize CAF heterogeneity and to study their interactions within the tumor microenvironment.\"}]","Cancer-Associated Fibroblasts in Gastrointestinal Cancers - Unveiling Their Dynamic Roles in the Tumor Microenvironment | PDF",1790224821,38]