[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-340899-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-340899-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","loss-of-lect2-promotes-ovarian-cancer-progression-by-inducing-cancer-invasiveness-and-facilitating-an-immunosuppressive-environment","Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment","","LECT2 is a multifunctional cytokine implicated in diverse diseases, including cancers. This study reports reduced serum LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 during disease progression in a syngeneic ID8 mouse model. In the murine EOC system, loss of Lect2 accelerates tumor progression by altering tumor cells and the tumor microenvironment. Mechanistically, Lect2 restrains invasive behavior and transcoelomic metastasis via c-Met signaling, while Lect2 downregulation increases and activates myeloid-derived suppressor cells, creating an immunosuppressive niche that suppresses T-cell activation and drives M2 macrophage polarization, impairing PD-1/PD-L1 blockade efficacy.",{"@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/loss-of-lect2-promotes-ovarian-cancer-progression-by-inducing-cancer-invasiveness-and-facilitating-an-immunosuppressive-environment/340899/",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/loss-of-lect2-promotes-ovarian-cancer-progression-by-inducing-cancer-invasiveness-and-facilitating-an-immunosuppressive-environment/340899.png","ImageObject",300,407,{"name":42,"@type":43},"Patrick","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What clinical observation links LECT2 to epithelial ovarian cancer progression?","Question",{"text":63,"@type":64},"Serum LECT2 levels are reduced in patients with epithelial ovarian cancer, and circulating Lect2 decreases as the disease progresses.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does loss of Lect2 influence EOC progression in the ID8 mouse model?",{"text":68,"@type":64},"Loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment.",{"name":70,"@type":61,"acceptedAnswer":71},"Through what mechanisms does Lect2 affect metastasis and immune suppression?",{"text":72,"@type":64},"Lect2 inhibits invasive phenotype and suppresses transcoelomic metastasis via c-Met signaling. Its downregulation increases and activates myeloid-derived suppressor cells, suppressing T-cell activation and shifting macrophages toward an M2 phenotype.","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},340899,1790812379,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"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":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},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":55,"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},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Oncogene [www.nature.com/onc](www.nature.com/onc)  \nARTICLE OPEN   \nLoss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment  \nChin-Jui Wu 1,2,3,11, Ke-Fan Pan 3,4,5,6,11, Ji-Qing Chen 7, Yu -Chen Tao1, Yu-Cheng Liu3, Bo-Rong Chen8, Ching Hsu1, Ming-Yang Wang8, Bor-Ching Sheu1, Michael Hsiao 9, Kuo-Tai Hua 3,10 ✉ and Lin-Hung Wei 1 ✉  \n© The Author(s) 2023  \n\n|  |  |  |\n| --- | --- | --- |\n|  | Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. Lect2 inhibited EOC cells’ invasive phenotype and suppressed EOC’s transcoelomic metastasis by targeting c-Met signaling. In addition, Lect2 downregulation induced the accumulation and activation of myeloid-derived suppressor cells (MDSCs) . This fostered an immunosuppressive microenvironment in EOC by inhibiting T-cell activation and skewing macrophages toward an M2 phenotype. The therapeutic efficacy of programmed cell death-1 (PD-1)/PD-L1 pathway blockade for the ID8 model was significantly hindered. Overall, our data highlight multiple functions of Lect2 during EOC progression and reveal a rationale for synergistic immunotherapeutic strategies by targeting Lect2 .\u003Cbr>Oncogene (2024) 43:511–523; [https://doi.org/10.1038/s41388-023-02918-w](https://doi.org/10.1038/s41388-023-02918-w) |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n\nGraphical Abstract  \nINTRODUCTION  \nEpithelial ovarian cancer (EOC) remains one of the most significant clinical challenges in medicine. Most EOC cases are discovered  \nwhen the primary tumor is disseminated via the transcoelomic route [1] . At staging laparotomy, approximately 70% of patients have multifocal intraperitoneal metastasis and malignant ascites.  \n1Department of Obstetrics and Gynecology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 2Department of Obstetrics and Gynecology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan. 3Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. 4Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 5Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 6Division of Colorectal Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 7Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. 8Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan. 9Genomics Research Center, Academia Sinica, Taipei, Taiwan. 10Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. 11These authors contributed equally: Chin-Jui Wu, Ke-Fan Pan. ✉ email: [kthua@ntu.edu.tw](kthua@ntu.edu.tw); [weilh1966@gmail.com](weilh1966@gmail.com)  \nReceived: 12 July 2023 Revised: 3 December 2023 Accepted: 5 December 2023  \nPublished online: 4 January 2024  \nC. Wu et al.  \n512  \nA B  \nSerum LECT2 (ng/ml)  \nSerum LECT2 (ng/ml)  \nC  \nLuminescence 5.0  \n4.0  \n3.0 x10 5  \n2.0  \nSerum Lect2 (ng/ml)  \n1.0 Radiance (p/sec/cm²/sr)  \nWeeks post ID8 inoculation  \nFig. 1 In vivo LECT2 concentration of EOC. A Comparison of serum levels of LECT2 protein ","cbCaibS4jZ3aYfTI","https://ap.wps.com/l/cbCaibS4jZ3aYfTI","pdf",4916090,13,"English","# Introduction\n## Clinical challenges in epithelial ovarian cancer (EOC)\n## Limits of immune checkpoint blockade (ICB)\n## Biological basis for low ICB response\n# LECT2 background and rationale","[{\"question\":\"What clinical observation links LECT2 to epithelial ovarian cancer progression?\",\"answer\":\"Serum LECT2 levels are reduced in patients with epithelial ovarian cancer, and circulating Lect2 decreases as the disease progresses.\"},{\"question\":\"How does loss of Lect2 influence EOC progression in the ID8 mouse model?\",\"answer\":\"Loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment.\"},{\"question\":\"Through what mechanisms does Lect2 affect metastasis and immune suppression?\",\"answer\":\"Lect2 inhibits invasive phenotype and suppresses transcoelomic metastasis via c-Met signaling. Its downregulation increases and activates myeloid-derived suppressor cells, suppressing T-cell activation and shifting macrophages toward an M2 phenotype.\"}]","Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment | PDF",1790039472,33]