[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-374237-105":59,"doc-detail-374237-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","dys-regulated-phosphatidylserine-externalization-as-a-cell-intrinsic-immune-escape-mechanism-in-cancer","Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer","","The negatively charged aminophospholipid phosphatidylserine (PS) is normally confined to the inner leaflet, but it becomes irreversibly exposed during apoptosis to drive efferocytosis-mediated elimination, and is reversibly exposed during immune and platelet activation. PS externalization depends on tightly regulated flippases and scramblases, and misregulation causes thrombosis and, when efferocytosis fails, autoimmunity such as systemic lupus erythematosus. In cancer and viral infection, stressed cells exhibit persistent PS surface exposure, promoting chronic immune evasion. This review synthesizes evidence linking dysregulated PS to cancer signaling, outlines mechanisms behind immune escape, and discusses PS-targeting therapeutic strategies, including rationale for adjuvant use with immune checkpoint therapy.",{"@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/dys-regulated-phosphatidylserine-externalization-as-a-cell-intrinsic-immune-escape-mechanism-in-cancer/374237/",{"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/dys-regulated-phosphatidylserine-externalization-as-a-cell-intrinsic-immune-escape-mechanism-in-cancer/374237.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does phosphatidylserine (PS) normally play in the plasma membrane?","Question",{"text":113,"@type":114},"PS is typically restricted to the inner leaflet of the plasma membrane under healthy conditions, maintaining membrane asymmetry and supporting key cell functions.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does dysregulated PS externalization contribute to disease?",{"text":118,"@type":114},"Improper PS externalization disrupts immune clearance and can trigger chronic thrombosis; when efferocytosis fails, it can also contribute to autoimmunity such as systemic lupus erythematosus.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is PS externalization important in cancer immune escape?",{"text":122,"@type":114},"In cancer, persistently exposed PS on diseased cells is proposed to reflect a cell intrinsic immune escape mechanism, enabling chronic immune evasion and signaling.","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},374237,1790638283,{"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":26},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Pulica et al.  \nCell Communication and Signaling (2025) 23:131 [https://doi.org/10.1186/s12964-025-02090-6](https://doi.org/10.1186/s12964-025-02090-6)  \nCell Communication and Signaling  \n REVIEW Open Access  \nDys-regulated  \nphosphatidylserine  \nexternalization as a cell intrinsic immune escape mechanism in cancer  \nRachael Pulica1, Ahmed Aquib1, Christopher Varsanyi1, Varsha Gadiyar1, Ziren Wang1, Trevor Frederick1, David C. Calianese 1, Bhumik Patel1, Kenneth Vergel de Dios 1, Victor Poalasin1, Mariana S. De Lorenzo2, Sergei V. Kotenko 1, Yi Wu3, Aizen Yang3, Alok Choudhary4, Ganapathy Sriram5 and Raymond B. Birge 1*  \nAbstract  \nThe negatively charged aminophospholipid, phosphatidylserine (PS), is typically restricted to the inner leaflet  \nof the plasma membrane under normal, healthy physiological conditions. PS is irreversibly externalized during apoptosis, where it serves as a signal for elimination by efferocytosis. PS is also reversibly and transiently externalized during cell activation such as platelet and immune cell activation. These events associated with physiological PS externalization are tightly controlled by the regulated activation offlippases and scramblases. Indeed, improper regulation of PS externalization results in thrombotic diseases such as Scott Syndrome, a defect in coagulation and thrombin production, and in the case of efferocytosis, can result in autoimmunity such as systemic lupus erythematosus (SLE) when PS-mediated apoptosis and efferocytosis fails. The physiological regulation of PS is also perturbed in cancer and during viral infection, whereby PS becomes persistently exposed on the surface of such stressed and diseased cells, which can lead to chronic thrombosis and chronic immune evasion. In this review, we summarize evidence for the dysregulation of PS with a main focus on cancer biology and the pathogenic mechanisms for immune evasion and signaling by PS, as well as the discussion of new therapeutic strategies aimed to target externalized PS. We posit that chronic PS externalization is a universal and agnostic marker for diseased tissues, and in cancer, likely reflects a cell intrinsic form of immune escape. The continued development of new therapeutic strategies for targeting PS also provides rationale for their co-utility as adjuvants and with immune checkpoint therapeutics.  \nKeywords Phosphatidylserine, P4 ATPase, Scramblases, PS receptors, Immune escape  \n*Correspondence: Raymond B. Birgebirgera@njms.rutgers  \n1 Department of Microbiology, Biochemistry and Molecular Genetics, Center for Cell Signaling, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA  \n2 Department of Cell Biology and Molecular Medicine, 185 South Orange Ave, Newark, NJ 07103, USA  \n3 Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Cyrus Tang Medical Institute, Soochow University, Suzhou, China  \n4 International Center for Public Health, Public Health Research Institute, Newark, NJ 07103, USA  \n5 Department Biological, Chemical and Environmental Sciences, Wheaton College, 26 E Main St, Norton, MA 02766, USA  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http:","cbCaijpLbZ2WiUKY","https://ap.wps.com/l/cbCaijpLbZ2WiUKY","pdf",5381694,24,"English","# Abstract\n# Phospholipid asymmetry and phosphatidylserine (PS) externalization mechanisms\n## Plasma membrane phospholipid asymmetry\n## Importance of PS asymmetry for membrane functions","[{\"question\":\"What role does phosphatidylserine (PS) normally play in the plasma membrane?\",\"answer\":\"PS is typically restricted to the inner leaflet of the plasma membrane under healthy conditions, maintaining membrane asymmetry and supporting key cell functions.\"},{\"question\":\"How does dysregulated PS externalization contribute to disease?\",\"answer\":\"Improper PS externalization disrupts immune clearance and can trigger chronic thrombosis; when efferocytosis fails, it can also contribute to autoimmunity such as systemic lupus erythematosus.\"},{\"question\":\"Why is PS externalization important in cancer immune escape?\",\"answer\":\"In cancer, persistently exposed PS on diseased cells is proposed to reflect a cell intrinsic immune escape mechanism, enabling chronic immune evasion and signaling.\"}]","Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer | PDF",1790201339]