[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-336687-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-336687-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","tertiary-lymphoid-structures-in-diseases-immune-mechanismsand-therapeutic-advances","Tertiary lymphoid structures in diseases: immune mechanismsand therapeutic advances","","Tertiary lymphoid structures (TLSs) are defined as lymphoid aggregates that arise in non-hematopoietic organs under pathological conditions and rely on interactions between LTi and LTo cells, coordinated by multiple cytokines. TLSs show marked heterogeneity and are linked to cancers, autoimmune disorders, transplant rejection, chronic inflammation, infection, and ageing, yet key mechanisms remain incomplete, including how maturation and localization shape immune function. The review synthesizes TLS composition, formation, disease associations, therapeutic relevance as markers of response and prognosis, and current detection and targeting approaches.",{"@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/tertiary-lymphoid-structures-in-diseases-immune-mechanismsand-therapeutic-advances/336687/",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/tertiary-lymphoid-structures-in-diseases-immune-mechanismsand-therapeutic-advances/336687.png","ImageObject",300,407,{"name":42,"@type":43},"Theodore","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are tertiary lymphoid structures (TLSs)?","Question",{"text":63,"@type":64},"TLSs are organized, nonencapsulated lymphoid aggregates formed in nonlymphoid tissues under pathological conditions after birth. They include germinal centers, surrounding T-cell areas, and distributed PANd+ high endothelial venules.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do TLSs form and what influences their development?",{"text":68,"@type":64},"TLS formation depends on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Chronic inflammation such as infections, autoimmune diseases, tissue transplants, and cancers typically drives TLS development.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic roles are discussed for TLSs?",{"text":72,"@type":64},"TLS presence correlates positively with immune checkpoint blockade efficacy, although the underlying mechanism is still unclear. The review also discusses TLSs as markers of therapeutic response and prognosis, and summarizes methods for detecting and targeting TLSs.","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},336687,1790117095,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":107,"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},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans)  \nREVIEW ARTICLE  \nOPEN  \nTertiary lymphoid structures in diseases: immune mechanismsand therapeutic advances  \nLianyu Zhao1,2, Song Jin 1,2, Shengyao Wang3, Zhe Zhang3, Xuan Wang 1,2, Zhanwei Chen1,2, Xiaohui Wang2, Shengyun Huang 1,2 ✉, Dongsheng Zhang 1,2 ✉ and Haiwei Wu 1,2 ✉  \n\n|  | Tertiary lymphoid structures (TLSs) are defined as lymphoid aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary lymphoid organs (SLOs), the formation of TLSs relies on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature of TLSs, which may lead to differences in their functions. Growing evidence suggests that TLSs are associated with various diseases, such as cancers, autoimmune diseases, transplant rejection, chronic inflammation, infection, and even ageing. However, the detailed mechanisms behind these clinical associations are not yet fully understood. The mechanisms by which TLS maturation and localization affect immune function are also unclear. Therefore, it is necessary to enhance the understanding of TLS development and function at the cellular and molecular level, which may allow us to utilize them to improve the immune microenvironment. In this review, we delve into the composition, formation mechanism, associations with diseases, and potential therapeutic applications of TLSs. Furthermore, we discuss the therapeutic implications of TLSs, such as their role as markers of therapeutic response and prognosis. Finally, we summarize various methods for detecting and targeting TLSs. Overall, we provide a comprehensive |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| understanding of TLSs and aim to develop more effective therapeutic strategies. |  |  |\n|  | Signal Transduction and Targeted Therapy (2024)9:225 ; [https://doi.org/10.1038/s41392-024-01947-5](https://doi.org/10.1038/s41392-024-01947-5) |  |\n|  |  |  |\n\nINTRODUCTION  \nTertiary lymphoid structures (TLSs) are organized, nonencapsulated aggregates of lymphoid cells that form in nonlymphoid tissues under pathological conditions after birth.1,2 TLSs mainly include germinal centers (GCs), surrounding T-cell areas, and distributed PANd+ high endothelial venules (HEVs) .3–5 TLSs typically form in response to chronic inflammation, such as infections, autoimmune diseases, tissue transplants, and cancers.6–12 Recent studies have found a positive correlation between the presence of TLSs and the efficacy of immune checkpoint blockade (ICB) therapy. However, the underlying mechanism remains unclear, and only a minority of patients benefit from this therapy.6, 13, 14 Moreover, the prognostic value of TLSs has been widely discussed. In conditions that require an enhanced immune response, such as cancer and infectious diseases, the presence and maturation of TLSs generally indicate more favorable outcomes.6, 15–19 Conversely, in autoimmune diseases and agerelated chronic inflammatory conditions, which involve the immune system attacking self-tissues, the emergence and maturation of TLSs are often associated with poorer prognoses.20–22 Therefore, TLSs can be seen as a double-edged sword. To fully harness the potential of TLSs, a comprehensive understanding of TLSs is urgently needed.  \nIn 1964, Ziff noticed similarities between inflamed rheumatoid synovial tissue and lymph nodes, where the primary immune  \nresponse occurs.23,24 In the early 1970s, Söderström et al. found that the structure of thyroid tissue in patients with Hashimoto’s thyroiditis resembled that of lymph nodes.24,25 In 1992, Louis Picker and Eugene Butcher formally introduced the concept of“tertiary lymphoid organs”","cbCaim6Gsd0ltHD7","https://ap.wps.com/l/cbCaim6Gsd0ltHD7","pdf",4519819,43,"English","# Introduction\n## Tertiary lymphoid structures (TLSs) in disease contexts\n# Formation and immune mechanisms\n## Cellular and molecular development pathways\n# Clinical associations and prognostic value\n## Links to cancers, autoimmunity, transplant rejection, chronic inflammation, and infection\n# Therapeutic implications\n## TLSs as biomarkers and targets\n# Detection and targeted strategies","[{\"question\":\"What are tertiary lymphoid structures (TLSs)?\",\"answer\":\"TLSs are organized, nonencapsulated lymphoid aggregates formed in nonlymphoid tissues under pathological conditions after birth. They include germinal centers, surrounding T-cell areas, and distributed PANd+ high endothelial venules.\"},{\"question\":\"How do TLSs form and what influences their development?\",\"answer\":\"TLS formation depends on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Chronic inflammation such as infections, autoimmune diseases, tissue transplants, and cancers typically drives TLS development.\"},{\"question\":\"What therapeutic roles are discussed for TLSs?\",\"answer\":\"TLS presence correlates positively with immune checkpoint blockade efficacy, although the underlying mechanism is still unclear. The review also discusses TLSs as markers of therapeutic response and prognosis, and summarizes methods for detecting and targeting TLSs.\"}]","Tertiary lymphoid structures in diseases: immune mechanismsand therapeutic advances | PDF",1790016164,108]