[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-385853-105":59,"doc-detail-385853-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-adaptor-protein-traf3-is-an-immune-checkpoint-that-inhibits-myeloid-derived-suppressor-cell-expansion","The adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion","","Myeloid-derived suppressor cells (MDSCs) expand abnormally in cancer and other pathological states, shaping immunosuppressive and inflammatory programs that enable metastasis and reduce therapy responsiveness. This study identifies the adaptor protein TRAF3 as a critical immune checkpoint limiting MDSC expansion. Traf3-deficient myeloid-specific mice show MDSC hyperexpansion during chronic inflammation, accelerating transplanted tumor growth and metastasis via altered T and NK cell phenotypes. Mixed bone marrow chimeras reveal both cell-intrinsic and cell-extrinsic inhibition. Mechanistically, the work delineates GM-CSF-STAT3-TRAF3-PTP1B signaling in MDSCs and a TLR4-TRAF3-CCL22-CCR4-G-CSF axis in inflammatory macrophages and monocytes that coordinately controls MDSC expansion.",{"@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-adaptor-protein-traf3-is-an-immune-checkpoint-that-inhibits-myeloid-derived-suppressor-cell-expansion/385853/",{"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-adaptor-protein-traf3-is-an-immune-checkpoint-that-inhibits-myeloid-derived-suppressor-cell-expansion/385853.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main discovery about TRAF3 in this study?","Question",{"text":113,"@type":114},"TRAF3 is identified as a novel immune checkpoint that critically restrains myeloid-derived suppressor cell (MDSC) expansion.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does myeloid-specific Traf3 deficiency affect MDSCs and tumor outcomes?",{"text":118,"@type":114},"Myeloid cell-specific Traf3-deficient mice exhibit MDSC hyperexpansion during chronic inflammation, which accelerates growth and metastasis of transplanted tumors, linked to altered T cell and NK cell phenotypes.",{"name":120,"@type":111,"acceptedAnswer":121},"Which signaling pathways are reported to control MDSC expansion?",{"text":122,"@type":114},"The study highlights a GM-CSF-STAT3-TRAF3-PTP1B axis in MDSCs and a TLR4-TRAF3-CCL22-CCR4-G-CSF axis in inflammatory macrophages and monocytes that coordinately regulate MDSC expansion.","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},385853,1790748825,{"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":46,"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":31},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","TYPE Original Research PUBLISHED 03 May 2023  \nDOI 10.3389/fimmu.2023.1167924  \nOPEN ACCESS  \nEDITED BY  \nYulia Nefedova,  \nWistar Institute, United States  \nREVIEWED BY  \nSergei Kusmartsev,  \nUniversity of Florida, United States Nik Theodoros Georgopoulos,  \nUniversity of Huddersfield, United Kingdom Erika Adriana Eksioglu,  \nMoffitt Cancer Center, United States  \n*CORRESPONDENCE Ping Xie  \n [xie@dls.rutgers.edu](xie@dls.rutgers.edu)  \nRECEIVED 17 February 2023  \nACCEPTED 20 April 2023  \nPUBLISHED 03 May 2023  \nCITATION  \nZhu S, Lalani AI, Jin J, Sant’Angelo D, Covey LR, Liu K, Young HA, OstrandRosenberg S and Xie P (2023) The adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion.  \nFront. Immunol. 14:1167924 .  \ndoi: 10.3389/fimmu.2023.1167924  \nCOPYRIGHT  \n© 2023 Zhu, Lalani, Jin, Sant’Angelo, Covey, Liu, Young, Ostrand-Rosenberg and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nThe adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion  \nSining Zhu 1,2, Almin I. Lalani 1,2, Juan Jin 1,3, Derek Sant’Angelo 4,5,6, Lori R. Covey 1,6, Kebin Liu 7, Howard A. Young 8, Suzanne Ostrand-Rosenberg 9 and Ping Xie 1,6*  \n1 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, United States,  \n2Graduate Program in Cellular and Molecular Pharmacology, Rutgers University, Piscataway, NJ, United States, 3 Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China, 4Child Health Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States,  \n5 Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States, 6 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States, 7 Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, United States, 8 Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD, United States,  \n9 Department of Biological Sciences, The University of Maryland, Baltimore County, Baltimore, MD, United States  \nMyeloid-derived suppressor cells (MDSCs) are aberrantly expanded in cancer patients and under other pathological conditions. These cells orchestrate the immunosuppressive and inflammatory network to facilitate cancer metastasis and mediate patient resistance to therapies, and thus are recognized as a prime therapeutic target of human cancers. Here we report the identification of the adaptor protein TRAF3 as a novel immune checkpoint that critically restrains MDSC expansion. We found that myeloid cell-specific Traf3-deficient (MTraf3-/-) mice exhibited MDSC hyperexpansion during chronic inflammation. Interestingly, MDSC hyperexpansion in M-Traf3-/ - mice led to accelerated growth and metastasis of transplanted tumors associated with an altered phenotype of T cells and NK cells. Using mixed bone marrow chimeras, we demonstrated that TRAF3 inhibited MDSC expansion via both cell-intrinsic and cell-extrinsic mechanisms. Furthermore, we elucidated a GM-CSF-STAT3-TRAF3-PTP1B signaling axis in MDSCs and a novel TLR4-TRAF3-CCL22-CCR4-G-CSF axis acting in inflammatory macrophages and monocytes that coordinately control MDSC expansion during chronic inflammation. Taken together, our findings provide novel insights into the complex regulatory mechanisms of MDSC expansion and open up unique perspectives for the design of new therapeutic strategies that aim to target MDSCs in cancer pati","cbCailE05VcUxGB6","https://ap.wps.com/l/cbCailE05VcUxGB6","pdf",10464986,"English","# Highlights\n## Immune checkpoint role of TRAF3\n## In vivo effects of TRAF3 deficiency\n## TRAF3 signaling axes in immune cells\n# Introduction\n## Cancer immunotherapies and limitations\n## Role of MDSCs in immunosuppression\n## Need for targeting MDSCs","[{\"question\":\"What is the main discovery about TRAF3 in this study?\",\"answer\":\"TRAF3 is identified as a novel immune checkpoint that critically restrains myeloid-derived suppressor cell (MDSC) expansion.\"},{\"question\":\"How does myeloid-specific Traf3 deficiency affect MDSCs and tumor outcomes?\",\"answer\":\"Myeloid cell-specific Traf3-deficient mice exhibit MDSC hyperexpansion during chronic inflammation, which accelerates growth and metastasis of transplanted tumors, linked to altered T cell and NK cell phenotypes.\"},{\"question\":\"Which signaling pathways are reported to control MDSC expansion?\",\"answer\":\"The study highlights a GM-CSF-STAT3-TRAF3-PTP1B axis in MDSCs and a TLR4-TRAF3-CCL22-CCR4-G-CSF axis in inflammatory macrophages and monocytes that coordinately regulate MDSC expansion.\"}]","The adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion | PDF",1790271254]