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Dysregulation of Eph receptors and ephrin ligands contributes to cancer, including skin malignancies such as squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Altered Eph/ephrin expression affects motility, adhesion, angiogenesis, and can reshape the tumor microenvironment by modulating immune-cell infiltration and T-cell activation, promoting immune evasion. The review evaluates Eph/ephrin signaling as a therapeutic target to inhibit tumor invasion, immune suppression, and metastatic progression.",{"@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/ephephrin-mediated-immune-modulation-a-potential-therapeutic-target/373266/",{"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/ephephrin-mediated-immune-modulation-a-potential-therapeutic-target/373266.png","ImageObject",300,407,{"name":92,"@type":93},"\tCallum ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",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 does Eph/ephrin signaling play in normal biology?","Question",{"text":113,"@type":114},"Eph/ephrin signaling coordinates cell-cell interactions that regulate migration, proliferation, and adhesion.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How can Eph/ephrin dysregulation contribute to skin cancers?",{"text":118,"@type":114},"Aberrant Eph receptor and ephrin ligand expression can increase tumor motility, reduce adhesion, enhance angiogenesis, and support invasion and metastasis.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is Eph/ephrin signaling considered a therapeutic target for skin cancer metastasis?",{"text":122,"@type":114},"Targeting the pathway may suppress tumor cell invasion and angiogenesis and help counter immune evasion by improving immune surveillance and T-cell activation.","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},373266,1790226800,{"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},137451211410,"https://ap-avatar.wpscdn.com/avatar/2000bb0a9246f588df?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786362646172706240","TYPE Review  \nPUBLISHED 22 April 2025  \nDOI 10.3389/fimmu.2025.1539567  \nOPEN ACCESS  \nEDITED BY  \nDomenico Mallardo,  \nG. Pascale National Cancer Institute Foundation (IRCCS), Italy  \nREVIEWED BY  \nTracey Lamb,  \nThe University of Utah, United States Sophia Koutsogiannaki,  \nHarvard Medical School, United States  \n*CORRESPONDENCE  \nPanagiotis Kratimenos  \n panagiotis. kratimenos@ [childrensnational.org](childrensnational.org)  \n†These authors have contributed equally to this work  \nRECEIVED 04 December 2024  \nACCEPTED 24 March 2025  \nPUBLISHED 22 April 2025  \nCITATION  \nGiannopoulos K, Karikis I, Byrd C, Sanidas G, Wolff N, Triantafyllou M, Simonti G, Vidva R, Koutroulis I, Theocharis S and Kratimenos P (2025) Eph/ephrin-mediated immune modulation: a potential therapeutic target.  \nFront. Immunol. 16:1539567 .  \ndoi: 10.3389/fimmu.2025.1539567  \nCOPYRIGHT  \n© 2025 Giannopoulos, Karikis, Byrd, Sanidas, Wolff, Triantafyllou, Simonti, Vidva, Koutroulis, Theocharis and Kratimenos. This is an openaccess 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.  \nEph/ephrin-mediated immune modulation:  \na potential therapeutic target  \nKonstantinos Giannopoulos 1†, Ioannis Karikis 1†, Chad Byrd 2, Georgios Sanidas 2, Nora Wolff 2, Maria Triantafyllou 2, Gabriele Simonti 2, Robinson Vidva 2, Ioannis Koutroulis 2,3, Stamatios Theocharis 1 and Panagiotis Kratimenos 2,3*  \n1 National and Kapodistrian University of Athens School of Medicine, Athens, Greece, 2Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, United States, 3 Department of Pediatrics, George Washington University, School of Medicine and Health Sciences, Washington, DC, United States  \nEph/ephrin signaling, a complex network of cell-cell interactions, plays a pivotal role in regulating various biological processes, including cell migration, proliferation, and adhesion. Dysregulation of this signaling pathway has been implicated in various types of cancer. In skin cancers such as squamous cell carcinoma, basal cell carcinoma, and malignant melanoma, Eph/ephrin signaling promotes tumor invasion and metastasis. Aberrant expression of Eph receptors and ephrin ligands can lead to increased cell motility, reduced cell adhesion, and enhanced angiogenesis. Furthermore, Eph/ephrin signaling can significantly impact the tumor microenvironment by modulating the infiltration and activation of immune cells, particularly T cells. Dysregulated Eph/ephrin expression can impair immune surveillance mechanisms, leading to immune evasion and tumor progression. For instance, certain ephrin ligands can inhibit T-cell activation and promote immunosuppressive conditions within the tumor microenvironment. Targeting Eph/ephrin signaling offers a promising therapeutic approach to combating skin cancer metastasis. By disrupting these signaling pathways, tumor cell invasion, angiogenesis, and immune evasion can be inhibited. This could lead to improved therapeutic outcomes for patients with skin cancer.  \nKEYWORDS  \nskin cancer, skin cancer therapy, Eph/ephrin receptor system, melanoma, basal cell carcinoma, squamous cell carcinoma  \nIntroduction  \nSkin cancer is among the most prevalent malignancies worldwide, with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma being the most common forms (1) . Melanoma is the most aggressive and deadly form of skin cancer. The mainstay of treatment for skin cancer is surgical excision (2) . For nonmelanoma skin cancer, such as BCC and SCC, excision of the tumor with a margin of healthy tissue is usually sufficient. For ","cbCaicGSueaLhjTT","https://ap.wps.com/l/cbCaicGSueaLhjTT","pdf",1278043,11,"English","# Introduction\n## Eph/ephrin signaling and immune modulation in skin cancer\n## Therapeutic targeting of Eph/ephrin signaling","[{\"question\":\"What role does Eph/ephrin signaling play in normal biology?\",\"answer\":\"Eph/ephrin signaling coordinates cell-cell interactions that regulate migration, proliferation, and adhesion.\"},{\"question\":\"How can Eph/ephrin dysregulation contribute to skin cancers?\",\"answer\":\"Aberrant Eph receptor and ephrin ligand expression can increase tumor motility, reduce adhesion, enhance angiogenesis, and support invasion and metastasis.\"},{\"question\":\"Why is Eph/ephrin signaling considered a therapeutic target for skin cancer metastasis?\",\"answer\":\"Targeting the pathway may suppress tumor cell invasion and angiogenesis and help counter immune evasion by improving immune surveillance and T-cell activation.\"}]","Eph/ephrin-mediated immune modulation - a potential therapeutic target | PDF",1790198442,28]