[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332061-105":59,"doc-detail-332061-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","glutamine-promotes-human-cd8-t-cells-and-counteracts-imiquimod-induced-t-cell-hyporesponsiveness","Glutamine promotes human CD8+ T cells and counteracts imiquimod-induced T cell hyporesponsiveness","","Glutamine (Gln) is a major extracellular amino acid in keratinocyte-derived skin cancers and enhances IFN-γ production by human CD8+ T cells. The study analyzes amino acid composition in interstitial fluids and examines T cell responses using primary human cell and tissue models. Imiquimod (IMQ) down-regulates metabolic regulators c-MYC and mTORC1 and amino acid transport and intracellular pools, reducing proliferation and IFN-γ while increasing GzB; Gln restores IFN-γ production in IMQ-treated CD8+ T cells, suggesting Gln metabolism as a therapeutic route for KDSCs.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/glutamine-promotes-human-cd8-t-cells-and-counteracts-imiquimod-induced-t-cell-hyporesponsiveness/332061/",{"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/glutamine-promotes-human-cd8-t-cells-and-counteracts-imiquimod-induced-t-cell-hyporesponsiveness/332061.png","ImageObject",300,407,{"name":92,"@type":93},"Aurora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-12","2026-09-21",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 effect does glutamine have on human CD8+ T cells?","Question",{"text":113,"@type":114},"Glutamine promotes interferon gamma (IFN-γ) production in human CD8+ T cells without inducing granzyme B (GzB) expression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does imiquimod alter CD8+ T cell metabolism and function?",{"text":118,"@type":114},"Imiquimod down-regulates c-MYC and mTORC1, amino acid transporter ASCT2, and intracellular amino acids in T cells, leading to reduced proliferation and IFN-γ expression with increased GzB.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is glutamine relevant as a potential treatment strategy for keratinocyte-derived skin cancers?",{"text":122,"@type":114},"Glutamine metabolism can be harnessed because it is sufficient to promote IFN-γ production in imiquimod-treated T cells, counteracting IMQ-induced hyporesponsiveness.","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},332061,1790012908,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"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,"preview_page_count":4},4810365810221,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","iScience  \nll  \nOPEN ACCESS  \nArticle  \nGlutamine promotes human CD8 + T cells and counteracts imiquimod-induced T cell hyporesponsiveness  \nLuisa Bopp, Maria Lope´z Martinez, Clara Schumacher,..., Susanne Brodesser, Ramon I. Klein Geltink, Mario Fabri  \n[mario.fabri@uk-koeln.de](mario.fabri@uk-koeln.de)  \nHighlights  \nGln is an abundant extracellular amino acid in cutaneous human (pre) -cancer  \nGln enhances IFN-g production by human CD8+ T cells  \nImiquimod perturbs CD8+ T cell AA metabolism, IFNg production, and proliferation  \nGln is sufficient to promote IFN-g production in imiquimod-treated CD8+ T cells  \nBopp et al., iScience 27, 109767 May 17, 2024 ª 2024 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/](https://doi.org/10.1016/)[ ](https://doi.org/10.1016/)[j.isci.2024.109767](j.isci.2024.109767)  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nGlutamine promotes human CD8 + T cells and counteracts imiquimod-induced T cell hyporesponsiveness  \nLuisa Bopp, 1 Maria Lope´z Martinez, 1 Clara Schumacher, 1 Robert Seitz, 1 Manuel Huerta Arana, 1  \nHenning Klapproth, 1 Dominika Lukas, 1 Ju Hee Oh,2,3 Daniela Neumayer, 1 Jan W. Lackmann,4 Stefan Mueller,5 Esther von Stebut, 1 Bent Brachvogel,5,6,7,8 Susanne Brodesser,8 Ramon I. Klein Geltink,2,3 and Mario Fabri 1,5,9,*  \nSUMMARY  \nT cells protect tissues from cancer. Although investigations in mice showed that amino acids (AA) critically regulate T cell immunity, this remains poorly understood in humans. Here, we describe the AA composition of interstitial fluids in keratinocyte-derived skin cancers (KDSCs) and study the effect of AA on T cells using models of primary human cells and tissues. Gln contributed to 􀀁 15% of interstitial AAs and promoted interferon gamma (IFN-g), but not granzyme B (GzB) expression, in CD8+ T cells. Furthermore, the Toll-like receptor 7 agonist imiquimod (IMQ), a common treatment for KDSCs, down-regulated the metabolic gatekeepers c-MYC and mTORC1, as well as the AA transporter ASCT2 and intracellular Gln, Asn, Ala, and Asp in T cells. Reduced proliferation and IFN-g expression, yet increased GzB, paralleled IMQ effects on AA. Finally, Gln was sufficient to promote IFN-g-production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.  \nINTRODUCTION  \nThe ability of CD8+ T cells to fight in situ and invasive cancer is pivotal to human skin homeostasis. Amino acids (AA) constitute key nutrients not only for tumor cells but also for T cells. They have essential roles in numerous cellular pathways, including activation of key signaling cascades, building blocks for protein synthesis, energy regeneration, redox homeostasis, and posttranscriptional modifications. It has become increasingly clear that AA support T cell function in cancer immunity.1–10 Meanwhile, competition for nutrients between tumor cells and immune cells shapes the functionality of immune cell subsets in tissues,2,5 and increasing evidence shows that the composition and quantity of intracellular and extracellular AA pools determines T cell fate and function.1–10 Although the vast majority of evidence comes from investigations in mouse models, there is limited knowledge regarding AA availability and those factors regulating AA utilization by human CD8+ T cells in skin malignancies.  \nBasal cell carcinoma (BCC) and squamous cell carcinoma (SCC) constitute keratinocyte-derived skin cancers (KDSCs), which, in sum, represent the most common human cancer.11 At an early stage, KDSCs show a slowly progressive course. Moreover, the sequential development from pre-cancer lesions, termed actinic keratosis, to invasive cancer is highly characteristic for SCC.12 In early KDSCs, imiquimod (IMQ), a synthetic Toll-like receptor 7 (TLR7) agonist, constitutes a frequently used destructive local therapy.12, 13 Although keratinocytes do not express TLR7,14–16 the TLR7-mediated activation of plasmacytoid dendritic cells (pDCs) results in the induc","cbCaiqmAAo6WEGkK","https://ap.wps.com/l/cbCaiqmAAo6WEGkK","pdf",3756218,"English","# Highlights\n## Key findings on glutamine and IFN-γ\n## Effects of imiquimod on CD8+ T cell metabolism\n# Summary\n# Introduction\n## Role of amino acids in CD8+ T cell cancer immunity\n## Keratinocyte-derived skin cancers and IMQ therapy\n## Study aim and approach","[{\"question\":\"What effect does glutamine have on human CD8+ T cells?\",\"answer\":\"Glutamine promotes interferon gamma (IFN-γ) production in human CD8+ T cells without inducing granzyme B (GzB) expression.\"},{\"question\":\"How does imiquimod alter CD8+ T cell metabolism and function?\",\"answer\":\"Imiquimod down-regulates c-MYC and mTORC1, amino acid transporter ASCT2, and intracellular amino acids in T cells, leading to reduced proliferation and IFN-γ expression with increased GzB.\"},{\"question\":\"Why is glutamine relevant as a potential treatment strategy for keratinocyte-derived skin cancers?\",\"answer\":\"Glutamine metabolism can be harnessed because it is sufficient to promote IFN-γ production in imiquimod-treated T cells, counteracting IMQ-induced hyporesponsiveness.\"}]","Glutamine promotes human CD8+ T cells and counteracts imiquimod-induced T cell hyporesponsiveness | PDF",1789996555]