[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-383024-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-383024-en":130},{"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","edil3-as-an-angiogenic-target-of-immune-exclusion-following-checkpoint-blockade","EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade","","Immune checkpoint blockade (ICB) is standard care for several solid tumors, and combining ICB with antiangiogenic agents has shown therapeutic benefit. To clarify mechanistic synergies, sera from long-term responding patients treated with ipilimumab and bevacizumab were screened, identifying high-titer EDIL3 (EGF-like repeats and discoidin I–like domains) antibodies linked to favorable outcomes. EDIL3 was associated with immune exclusion signatures, suggesting cancer-associated fibroblasts as a source. Analyses and experiments indicated EDIL3 ties to pan-fibroblast TGFb responses, angiogenic programs, TGFb-driven EMT, and impaired T-cell migration via disrupted LFA-1/ICAM-1 interactions.",{"@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/edil3-as-an-angiogenic-target-of-immune-exclusion-following-checkpoint-blockade/383024/",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/edil3-as-an-angiogenic-target-of-immune-exclusion-following-checkpoint-blockade/383024.png","ImageObject",300,407,{"name":42,"@type":43},"Elsa","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-25","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What treatment approach does the document study, and why is it relevant?","Question",{"text":63,"@type":64},"The document examines immune checkpoint blockade (ICB) and the added effect of antiangiogenic therapy. It focuses on how combining these modalities can improve efficacy and overcome resistance in solid tumors.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was EDIL3 identified as a clinically relevant target?",{"text":68,"@type":64},"Researchers screened sera from long-term responding patients treated with ipilimumab plus bevacizumab using protein arrays. They found a high-titer antibody response against EDIL3 correlated with favorable clinical outcomes.",{"name":70,"@type":61,"acceptedAnswer":71},"What mechanisms link EDIL3 to immune exclusion and angiogenesis?",{"text":72,"@type":64},"Tumor immune dysfunction and exclusion analysis associated EDIL3 with immune exclusion signatures, including reduced cytotoxic immune cell infiltration and nonresponse to ICB. Additional analyses and in vitro work connected EDIL3 to TGFb signaling in fibroblast programs, angiogenic enrichment, EMT induction, and disrupted LFA-1/ICAM-1 interactions that can impair T-cell trafficking.","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},383024,1790738824,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,109,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"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},137455077381,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade  \nSaba Tabasum1,2,3, Dinesh Thapa1,2,3, Anita Giobbie-Hurder3,4, Jason L. Weirather5,6, Marco Campisi1, Pieter J. Schol7, Xiaoyu Li1,2,3, Jingjing Li1,2,3, Charles H. Yoon8, Michael P. Manos1,2,3, David A. Barbie1, and F. Stephen Hodi1,2,3  \nABSTRACT  \n◥  \nImmune checkpoint blockade (ICB) has become the standard of care for several solid tumors. Multiple combinatorial approaches have been studied to improve therapeutic efficacy. The combination of antiangiogenic agents and ICB has demonstrated efficacy in several cancers. To improve the mechanistic understanding of synergies with these treatment modalities, we performed screens of sera from long-term responding patients treated with ipilimumaband bevacizumab. We discovered a high-titer antibody response against EGF-like repeats and discoidin I–like domains protein 3 (EDIL3) that correlated with favorable clinical outcomes. EDIL3 isan extracellular protein, previously identified as a marker of poor prognosis in various malignancies. Our Tumor Immune Dysfunction and Exclusion analysis predicted that EDIL3was associatedwith immune exclusion signatures for cytotoxic immune cell infiltration and nonresponse to ICB. Cancer-associated fibroblasts (CAF) were predicted as the source of EDIL3 in immune exclusion–related cells.  \nFurthermore, The Cancer GenomeAtlas Skin Cutaneous Melanoma (TCGA-SKCM) and CheckMate 064 data analyses correlated high levels of EDIL3 with increased pan-fibroblast TGFb response, enrichment of angiogenic signatures, and induction of epithelialto-mesenchymal transition. Our in vitro studies validated EDIL3 overexpression and TGFb regulation in patient-derived CAFs. In pretreatment serum samples from patients, circulating levels of EDIL3 were associated with circulating levels of VEGF, and like VEGF, EDIL3 increased the angiogenic abilities of patientderived tumor endothelial cells (TEC) . Mechanistically, threedimensional microfluidic cultures and two-dimensional transmigration assays with TEC endorsed EDIL3-mediated disruption of the lymphocyte function-associated antigen-1 (LFA-1)– ICAM-1 interaction as a possible means of T-cell exclusion. We propose EDIL3 as a potential target for improving the transendothelial migration of immune cells and efficacy of ICB therapy.  \nIntroduction  \nImmune checkpoint blockade (ICB) has become the standard of care for numerous malignancies, including melanoma, for which approximately 50% of patients with metastatic disease receive benefits(1). Combinatorial approaches to improve outcomesand overcome treatment resistance are sought for a sizeable patient population with unmet needs. The immune system is known to have an active interplay with the vascular system, as it is the gateway to the tumor microenvironment (TME) . Angiogenic factors have demonstrated immune suppression capabilities, and tumor blood vessels may limit the access of immune effector cells to the TME. Innovative strategies, including  \n1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 2Melanoma Disease Center, DanaFarber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 3Center for Immuno-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 4Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts. 5Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts. 6Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 7Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands. 8Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts.  \nCorresponding Author: F. Stephen Hodi, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 . E-mail: [stephen_hodi@dfci.harvard.edu](stephen_hodi@dfci.harvard.edu)","cbCaiipMGxSy1h2G","https://ap.wps.com/l/cbCaiipMGxSy1h2G","pdf",16304615,15,"English","# Abstract\n# Introduction\n# Materials and Methods\n## Patients","[{\"question\":\"What treatment approach does the document study, and why is it relevant?\",\"answer\":\"The document examines immune checkpoint blockade (ICB) and the added effect of antiangiogenic therapy. It focuses on how combining these modalities can improve efficacy and overcome resistance in solid tumors.\"},{\"question\":\"How was EDIL3 identified as a clinically relevant target?\",\"answer\":\"Researchers screened sera from long-term responding patients treated with ipilimumab plus bevacizumab using protein arrays. They found a high-titer antibody response against EDIL3 correlated with favorable clinical outcomes.\"},{\"question\":\"What mechanisms link EDIL3 to immune exclusion and angiogenesis?\",\"answer\":\"Tumor immune dysfunction and exclusion analysis associated EDIL3 with immune exclusion signatures, including reduced cytotoxic immune cell infiltration and nonresponse to ICB. Additional analyses and in vitro work connected EDIL3 to TGFb signaling in fibroblast programs, angiogenic enrichment, EMT induction, and disrupted LFA-1/ICAM-1 interactions that can impair T-cell trafficking.\"}]","EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade | PDF",1790253804,38]