[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332432-105":59,"doc-detail-332432-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","single-cell-and-spatial-transcriptome-analyses-reveal-tertiary-lymphoid-structures-linked-to-tumour-progression-and-immunotherapy-response-in-nasopharyngeal-carcinoma","Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma","","Single-cell and spatial transcriptome profiling in nasopharyngeal carcinoma maps tertiary lymphoid structures (TLS) and clarifies their links to tumour progression and immunotherapy. Analyses of 343,829 cells from biopsy and blood samples and spatial data from 15 tumours identify key TLS populations, including CXCL13+ cancer-associated fibroblasts, CXCL13+ stem-like CD8+ T cells, and B/T follicular helper cells. Germinal centre maturation generates plasma cells that intersperse with tumour aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ fibroblasts support B-cell adhesion and antibody production while triggering CXCL13+CD8+ T-cell activation that becomes exhausted within aggregates. TLS-related signatures correlate with prognosis and PD-1 blockade benefit, informing therapeutic strategies.",{"@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/single-cell-and-spatial-transcriptome-analyses-reveal-tertiary-lymphoid-structures-linked-to-tumour-progression-and-immunotherapy-response-in-nasopharyngeal-carcinoma/332432/",{"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/single-cell-and-spatial-transcriptome-analyses-reveal-tertiary-lymphoid-structures-linked-to-tumour-progression-and-immunotherapy-response-in-nasopharyngeal-carcinoma/332432.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",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 the main goal of the study in nasopharyngeal carcinoma?","Question",{"text":113,"@type":114},"To determine the cellular composition, formation, and function of tertiary lymphoid structures and relate them to tumour progression and immunotherapy response using single-cell and spatial transcriptomics.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which key cell populations are identified as essential for TLS in this work?",{"text":118,"@type":114},"The study highlights CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells.",{"name":120,"@type":111,"acceptedAnswer":121},"How do plasma cells and TLS activity affect tumour cells and treatment response?",{"text":122,"@type":114},"Germinal-centre reactions mature plasma cells that intersperse with tumour aggregates, promote apoptosis of EBV-related malignant cells, and enhance immunotherapy response; TLS-related signatures correlate with prognosis and PD-1 blockade outcomes.","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},332432,1790170738,{"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":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":146,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Article [https://doi.org/10.1038/s41467-024-52153-4](https://doi.org/10.1038/s41467-024-52153-4)  \nSingle-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response innasopharyngeal carcinoma  \nReceived: 13 July 2023  \n\n| Accepted: 22 August 2024 |\n| --- |\n| |\n| Check for updates |\n\nYang Liu1,10, Shuang-Yan Ye2,10, Shuai He 1,10, Dong-Mei Chi 1,3,10,  \nXiu-Zhi Wang1,10, Yue-Feng Wen4, Dong Ma1, Run-Cong Nie1, Pu Xiang1, You Zhou1, Zhao-Hui Ruan1, Rou-Jun Peng1, Chun-Ling Luo 1, Pan-Pan Wei1, Guo-Wang Lin5, Jian Zheng 1, Qian Cui6, Mu-Yan Cai 1, Jing-Ping Yun 1, Junchao Dong7, Hai-Qiang Mai 1, Xiaojun Xia 1 & Jin-Xin Bei 1,8,9   \nTertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structurerelated cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.  \nImmune cell infiltration is a common pathological observation in cancer, where tumoral, immune, and stromal cells, as well as extracellular components, are assembled to form a tumour microenvironment (TME). The organisation of these components is essential to an effective immunity against tumour1. Tertiary lymphoid structure (TLS) represents such a well-organised ectopic compartment of immune cells that develops in inflamed, infected, or tumoral tissues2,3. Initially, both T and B cell zones are characterised in TLS using  \nimmunohistochemistry (IHC) assays4. Subsequently, several studies reveal that TLSs also contain antigen-presenting cells (APCs) as regulators andstromal cells as supportive infrastructures5, in addition toT follicular helper(Tfh)cells and follicular dendritic cells(FDC)closetoB cells6. Recently, single-cell RNA sequencing and spatial transcriptomics studies reveal specific cell populations of TLS in tumours, such as CXCL13+ T-helper cells in ovarian cancer7, SEMA4A+ germinal centre (GC) B cells in head and neck squamous cell carcinoma8, and CXCL12+  \nA full list of affiliations appears at the end of the paper. e-mail: [beijx@sysucc.org.cn](beijx@sysucc.org.cn)  \nfibroblasts in renal cell cancer9. These findings suggest a complicated and heterogeneous composition of TLS in tumours from different technological perspectives, which await further investigations with larger sample sizes and cutting-edge technologies under higher resolution.  \nGC is a crucial feature of matured TLSs in tumours and is a wellknown compartment for the selective activation and amplification of B cell clonesand the production oflong-lived plasma cells6. Although the coexistence of GC B cells and tumour-infiltrating B or plasma cells has been demonstrated in multiple tumours9–11, little is known about the dynamic features of GC reaction and developmental trajectories of B cells within the tumours, especially at TLSs. A recent study has demonstrated GC B cells characterised by a continuum of gene expression states spanning the dark-light zone axis12,13. Apart from GC reaction, multiple cellular components, in","cbCaijITzyE9FL0r","https://ap.wps.com/l/cbCaijITzyE9FL0r","pdf",5580758,22,"English","# Introduction\n## Tumour microenvironment and TLS significance\n# Methods and Study Design\n## Single-cell and spatial transcriptome profiling in NPC\n# Key Findings\n## Essential TLS cell populations\n## Germinal centre maturation and plasma-cell function\n## CXCL13+ fibroblast, B-cell, and CD8+ T-cell interactions\n## Clinical correlations with prognosis and PD-1 blockade response\n# Background and Rationale\n## GC reaction and TLS composition in tumours\n## Unresolved questions in human tumour TLS dynamics","[{\"question\":\"What is the main goal of the study in nasopharyngeal carcinoma?\",\"answer\":\"To determine the cellular composition, formation, and function of tertiary lymphoid structures and relate them to tumour progression and immunotherapy response using single-cell and spatial transcriptomics.\"},{\"question\":\"Which key cell populations are identified as essential for TLS in this work?\",\"answer\":\"The study highlights CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells.\"},{\"question\":\"How do plasma cells and TLS activity affect tumour cells and treatment response?\",\"answer\":\"Germinal-centre reactions mature plasma cells that intersperse with tumour aggregates, promote apoptosis of EBV-related malignant cells, and enhance immunotherapy response; TLS-related signatures correlate with prognosis and PD-1 blockade outcomes.\"}]","Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma | PDF",1789998169,55]