[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-341705-105":59,"doc-detail-341705-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","the-nuclear-export-protein-xpo1-provides-a-peptide-ligand-for-natural-killer-cells","The nuclear export protein XPO1 provides a peptide ligand for natural killer cells","","XPO1 (Exportin-1/CRM1) is a nuclear export protein frequently overexpressed in cancer and explored as an anticancer target. The study identifies XPO1 as a target for natural killer (NK) cells and, via immunopeptidomics, finds a peptide derived from XPO1 that is recognized by the activating NK receptor KIR2DS2 with HLA-C. The peptide is endogenously processed and presented to activate NK cells specifically through this receptor. Evidence of NK cell infiltration substantially improves outcomes for certain cancers, supporting XPO1 as a bona fide tumor antigen for personalized NK-cell 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/the-nuclear-export-protein-xpo1-provides-a-peptide-ligand-for-natural-killer-cells/341705/",{"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/the-nuclear-export-protein-xpo1-provides-a-peptide-ligand-for-natural-killer-cells/341705.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-22",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 is XPO1 and why is it relevant to cancer therapy?","Question",{"text":113,"@type":114},"XPO1 is a nuclear export protein often overexpressed in cancer. Small-molecule XPO1 inhibitors have been used clinically as anticancer agents, and this work positions XPO1 as an NK-cell target as well.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How is the XPO1-derived peptide identified as an NK-cell ligand?",{"text":118,"@type":114},"Using immunopeptidomics, the study identifies an XPO1-derived peptide that can be recognized by the activating NK receptor KIR2DS2 in the context of HLA–C.",{"name":120,"@type":111,"acceptedAnswer":121},"Why does NK cell infiltration matter for cancer outcomes in this work?",{"text":122,"@type":114},"Although high XPO1 expression is commonly linked to poor prognosis, the study shows that outcomes for specific cancers can be substantially improved when there is concomitant evidence of NK-cell infiltration.","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},341705,1790326584,{"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":52,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","IMMUNOLOGY  \nThe nuclear export protein XPO1 provides a peptide ligand for natural killer cells  \nMatthew D. Blunt1, Hayden Fisher2,3,4, Ralf B. Schittenhelm5, Berenice Mbiribindi1,  \nRebecca Fulton1, Sajida Khan1, Laura Espana-Serrano1, Lara V. Graham1, Leidy Bastidas-Legarda, Daniel Burns1, Sophie M.S. Khakoo1, Salah Mansour1, Jonathan W. Essex3, Rochelle Ayala6, Jayajit Das7, Anthony W. Purcell6, Salim I. Khakoo1*  \nXPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as adriver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells. Using immunopeptidomics, we have identified a peptide derived from XPO1 that can be recognized by the activating NK cell receptor KIR2DS2 in the context of human leukocyte antigen–C. The peptide can be endogenously processed and presented to activate NK cells specifically through this receptor. Although high XPO1 expression in cancer is commonly associated with a poor prognosis, we show that the outcome of specific cancers, such as hepatocellular carcinoma, can be substantially improved if there is concomitant evidence of NK cell infiltration. We thus identify XPO1 as a bona fide tumor antigen recognized by NK cells that offers an opportunity for a personalized approach to NK cell therapy for solid tumors.  \ncopyright © 2024 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution license 4.0 (cc BY) .  \nINTRODUCTION  \nNatural killer (NK) cells are becoming increasingly recognized for their anticancer activity, and their functions are tightly controlled by a diverse repertoire of cell surface receptors (1) . One important family of NK cell receptors are the killer cell immunoglobulin-like receptors (KIRs), which form a polymorphic family of receptors with human leukocyte antigen (HLA) class I ligands (2) . KIRs have been implicated in susceptibility to, and the outcome of, many different cancers and thus contribute to heterogeneity within the innate immune response to malignancy (3–9) .  \nThe KIR can be activating or inhibitory. The HLA class I ligand specificities of the inhibitory KIR are relatively well defined, while the ligand specificities of the activating KIR have been much harder to identify ( 10) . Recent work has shown that activating KIR can have an HLA class I–restricted peptide specificity (11–15). While T cell receptors have a tight restriction on the peptide:HLA complexes that they bind, KIRs recognize families of peptide:HLA complexes in a motif-based manner allowing recognition of multiple different combination of peptide and HLA (16, 17) . We have recently shown that KIR2DS2 recognizes highly conserved flavivirus and hepatitis C peptides with an alanine-threonine sequence at the C-terminal −1 and −2 positions ofthe peptide in the context of HLA-C (12, 18) . We have also recently shown that targeting KIR2DS2 in vivo using a peptide:HLA-C–based strategy can increase NK cell activity against  \n1School of clinical and experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. 2School of cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. 3School of chemistry, Faculty of engineering and Physical Sciences, University of Southampton, Southampton, UK. 4School of Biological Sciences, Faculty of environmental and life Sciences, University of Southampton, Southampton, UK. 5Monash Proteomics & Metabolomics Platform, Biomedicine discovery institute and department of Biochemistry and Molecular Biology, Monash University, clayton, victoria, Australia. 6Biomedicine discovery institute and department of Biochemistry and Molecular Biology, Monash University, clayton, victoria, Australia. 7Steve and cindy Rasmussen institute for","cbCaibDdOUKOtZ70","https://ap.wps.com/l/cbCaibDdOUKOtZ70","pdf",1653457,"English","# Introduction\n## NK cell receptors and KIR-HLA ligand recognition","[{\"question\":\"What is XPO1 and why is it relevant to cancer therapy?\",\"answer\":\"XPO1 is a nuclear export protein often overexpressed in cancer. Small-molecule XPO1 inhibitors have been used clinically as anticancer agents, and this work positions XPO1 as an NK-cell target as well.\"},{\"question\":\"How is the XPO1-derived peptide identified as an NK-cell ligand?\",\"answer\":\"Using immunopeptidomics, the study identifies an XPO1-derived peptide that can be recognized by the activating NK receptor KIR2DS2 in the context of HLA–C.\"},{\"question\":\"Why does NK cell infiltration matter for cancer outcomes in this work?\",\"answer\":\"Although high XPO1 expression is commonly linked to poor prognosis, the study shows that outcomes for specific cancers can be substantially improved when there is concomitant evidence of NK-cell infiltration.\"}]","The nuclear export protein XPO1 provides a peptide ligand for natural killer cells | PDF",1790043265,25]