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Using murine and human models, B7-H4 was linked to epithelial cell status, PI3K-dependent regulation, altered EMT6 tumor sensitivity, and reduced tumor immune activation signaling. In human metastatic TNBC, B7-H4 correlated with improved survival with carboplatin plus anti-PD-L1, without early-stage benefit changes.",{"@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/epithelial-expressed-b7-h4-drives-differential-immunotherapy-response-in-murine-and-human-breast-cancer/336215/",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/epithelial-expressed-b7-h4-drives-differential-immunotherapy-response-in-murine-and-human-breast-cancer/336215.png","ImageObject",300,407,{"name":42,"@type":43},"Emma Wilson","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",17,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are immune checkpoint inhibitor plus chemotherapy regimens not effective for many TNBC patients?","Question",{"text":63,"@type":64},"The document states that although ICI (including anti-PD-1/PD-L1) plus chemotherapy is approved for metastatic and early-stage TNBC, most patients do not benefit.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study evaluate B7-H4 regulation and immune effects?",{"text":68,"@type":64},"It assessed murine and human breast cancer cells, using an immunocompetent anti-PD-L1–sensitive orthotopic mammary cancer model, with baseline and anti-PD-L1 treatment transcriptional changes.",{"name":70,"@type":61,"acceptedAnswer":71},"What association did the study find between B7-H4 and immunotherapy outcomes in mice versus humans?",{"text":72,"@type":64},"In mice, epithelial or cell-surface B7-H4 expression was linked to greater resistance to immunotherapy and reduced immune activation signaling, whereas in human metastatic TNBC treated with carboplatin plus anti-PD-L1, B7-H4 expression associated with a survival benefit; early breast cancer showed no change with chemotherapy plus anti-PD-1.","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},336215,1790479135,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","RESEARCH ARTICLE  [https://doi.org/10.1158/2767-9764.CRC-23-0468](https://doi.org/10.1158/2767-9764.CRC-23-0468)  OPEN ACCESS  \nEpithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer  \nElizabeth C. Wescott1 , Xiaopeng Sun2 , Paula Gonzalez-Ericsson2 , 3 , Ann Hanna3 , Brandie C. Taylor2 , Violeta Sanchez3 , Juliana Bronzini4 , Susan R. Opalenik3 , Melinda E. Sanders2 , 3 , Julia Wulfkuhle5 , Rosa I. Gallagher5 , Henry Gomez6 , Claudine Isaacs7 , Vijaya Bharti8 , John T. Wilson1 , 8 , Tarah J. Ballinger9 ,  \nCesar A. Santa-Maria10 , Payal D. Shah11 , Elizabeth C. Dees12 , Brian D. Lehmann2 , 3 , Vandana G. Abramson2 , 3 , Gillian L. Hirst13 , Lamorna Brown Swigart14 , Laura J. van ˈ t Veer14 , Laura J. Esserman13 , Emanuel F. Petricoin5 , Jennifer A. Pietenpol2 , 3 , 10 , 15 , and  \nJustin M. Balko1 , 2 , 3 , 16  \nCheck for updates  \nABSTRACT  \nCombinations of immune checkpoint inhibitors (ICI, including anti-PD- 1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers. We assessed murine and human breast cancer cells to identify regulation mechanisms of B7-H4 in vitro. We used an immunocompetent antiPD-L1–sensitive orthotopic mammary cancer model and induced ectopic expression of B7-H4 . We assessed therapy response and transcriptional changes at baseline and under treatment with anti-PD-L1 . We observed B7-H4 was highly associated with epithelial cell status and transcription factors and found to be regulated by PI3K activity. EMT6 tumors with cell-surface B7-H4 expression were more resistant to immunotherapy. In addition, tumor-infiltrating immune cells had reduced immune activation  \nsignaling based on transcriptomic analysis. Paradoxically, in human breast cancer, B7-H4 expression was associated with survival benefit for patients with metastatic TNBC treated with carboplatin plus anti-PD-L1 and was associated with no change in response or survival for patients with early breast cancer receiving chemotherapy plus anti-PD-1. While B7-H4 induces tumor resistance to anti-PD-L1 in murine models, there are alternative mechanisms of signaling and function in human cancers. In addition, the strong correlation of B7-H4 to epithelial cell markers suggests a potential regulatory mechanism of B7-H4 independent of PD-L1 .  \nSignificance: This translational study confirms the association of B7-H4 expression with a cold immune microenvironment in breast cancer and offers preclinical studies demonstrating a potential role for B7-H4 in suppressing response to checkpoint therapy. However, analysis of two clinical trials with checkpoint inhibitors in the early and metastatic settings argue against B7-H4 as being a mechanism of clinical resistance to checkpoints, with clear implications for its candidacy as a therapeutic target.  \n1 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. 2 Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. 3 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 4 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee. 5 Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia. 6 Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú . 7 Division of Hematology-Oncology, Department of Medicine, Georgetown University, Washington, District of Columbia. 8 Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee. ","cbCaictkA5Vn6mSq","https://ap.wps.com/l/cbCaictkA5Vn6mSq","pdf",25065749,15,"English","# Abstract\n# Introduction","[{\"question\":\"Why are immune checkpoint inhibitor plus chemotherapy regimens not effective for many TNBC patients?\",\"answer\":\"The document states that although ICI (including anti-PD-1/PD-L1) plus chemotherapy is approved for metastatic and early-stage TNBC, most patients do not benefit.\"},{\"question\":\"How did the study evaluate B7-H4 regulation and immune effects?\",\"answer\":\"It assessed murine and human breast cancer cells, using an immunocompetent anti-PD-L1–sensitive orthotopic mammary cancer model, with baseline and anti-PD-L1 treatment transcriptional changes.\"},{\"question\":\"What association did the study find between B7-H4 and immunotherapy outcomes in mice versus humans?\",\"answer\":\"In mice, epithelial or cell-surface B7-H4 expression was linked to greater resistance to immunotherapy and reduced immune activation signaling, whereas in human metastatic TNBC treated with carboplatin plus anti-PD-L1, B7-H4 expression associated with a survival benefit; early breast cancer showed no change with chemotherapy plus anti-PD-1.\"}]","Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer | PDF",1790014153,38]