[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-345965-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-345965-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":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","thyroid-cancer-from-potential-drivers-to-real-modulators-review","Thyroid Cancer - From Potential Drivers to Real Modulators - review","","Cancer immunotherapy has ushered in a shift from precision oncology focused on mutated genes to agnostic strategies that harness the immune system. A detailed grasp of the tumor immune microenvironment (TIME) can overcome challenges from cancer genetic diversity and evolutionary change. For thyroid cancer, progress is slower, with many studies emphasizing tumor genetics over TIME characterization. TIME, shaped by immune cells and signaling networks, evolves with growth and metastasis and is driven by genetic, metabolic, and therapeutic influences, defining clinical heterogeneity and informing immune-evasion counterstrategies.",{"@graph":14,"@context":72},[15,34,55],{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/thyroid-cancer-from-potential-drivers-to-real-modulators-review/345965/",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/thyroid-cancer-from-potential-drivers-to-real-modulators-review/345965.png","ImageObject",300,407,{"name":42,"@type":43},"Evangeline","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What is the central concept of this review on thyroid cancer therapy?","Question",{"text":62,"@type":63},"The review explains how targeting the tumor immune microenvironment (TIME) enables immunotherapies that can work beyond the tumor’s genetic origin, using an agnostic approach.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"Why has immunotherapy progress in thyroid cancer been relatively slow?",{"text":67,"@type":63},"Much of the research still concentrates on the genetic landscape of thyroid tumors rather than comprehensive exploration of their TIME and how it shapes immune evasion.",{"name":69,"@type":60,"acceptedAnswer":70},"What components make up the tumor immune microenvironment (TIME) in thyroid cancer?",{"text":71,"@type":63},"TIME includes immune cells such as macrophages, lymphocytes, natural killer cells, and mast cells, together with networks of signaling molecules that evolve alongside tumor growth and metastasis.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},345965,1790196318,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"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":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"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":26,"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},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","Review  \nThyroid Cancer: From Potential Drivers to Real Modulators  \nShafiya Imtiaz Rafiqi 1,2 and Juan Carlos Jaume 1,2, *  \nAcademic Editor: Michael Bouvet  \nReceived: 26 June 2026  \nRevised: 29 July 2026  \nAccepted: 31 July 2026  \nPublished: 1 August 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Medicine, Edward Hines Jr. VA Hospital, Hines, IL 60141, USA; [shafiyaimtiaz.rafiqi@va.gov](shafiyaimtiaz.rafiqi@va.gov)  \n2 Department of Medicine, Loyola University Chicago, Chicago, IL 60660, USA  \n* [Correspondence: juan.jaume@va.gov](Correspondence: juan.jaume@va.gov)  \nSimple Summary  \nUnleashing the immune microenvironment to cure cancer regardless of its genetic origin was once an unimaginable concept that is now a groundbreaking reality. While the notion of immunotherapy is not new, the modern era has seen a dramatic shift from targeting tumors by their genetic make-up to targeting the molecular features that fuel their growth in the tumor microenvironment—an approach known as “agnostic” therapy. This paradigm shift was made possible by decades of research into the intricate relationship between cancer cells and the surrounding tumor immune microenvironment (TIME) . Scientists uncovered how cancer cells exploit and manipulate the TIME to evade the immune system, leading to the development of therapies that block these escape mechanisms. We discuss here many of the genetic drivers thought to bring about thyroid cancer and immune modulators that allow or preclude its existence.  \nAbstract  \nThe advent of cancer immunotherapy opened a transformative era in oncology, shifting the focus from targeting mutated genes through precision oncology to harnessing the body’s immune system via agnostic therapies. This paradigm has demonstrated that a deeper understanding of the tumor immune microenvironment (TIME) can transcend the challenges posed by cancer’s genetic diversity and evolutionary dynamics. In the case of thyroid cancer, progress in immunotherapy has been comparatively slow. Much of the current research still centers on the genetic landscape of thyroid tumors rather than on comprehensive exploration of their TIME. The TIME, composed of immune cells such as macrophages, lymphocytes, natural killer cells, and mast cells, along with a network of signaling molecules, evolves alongside tumor growth and metastasis. It both influences and is influenced by genetic alterations, metabolic conditions, and therapeutic interventions. This dynamic crosstalk defines the clinical and biological heterogeneity of thyroid cancers; from the aggressive anaplastic thyroid carcinoma (ATC) to the more indolent papillary thyroid carcinoma (PTC) . Mapping the spatial and temporal changes within the TIME offers the opportunity to design therapies that counter immune evasion and enhance treatment response. As understanding of the tumor microenvironment deepens, thyroid cancer therapy is undergoing a major shift; from strategies aimed merely at genetic mutations to integrated, combinational approaches incorporating personalized immunotherapy. Building on recent findings, which detail immune cell composition and therapeutic implications in thyroid malignancies, this review expands on the molecular and cellular mechanisms shaping the microenvironment. We highlight how oncogenic signaling, stromal remodeling, and metabolic reprogramming coordinate to influence tumor immunity, and we explore emerging strategies that aim to reengineer the tumor microenvironment for improved therapeutic outcomes.  \nKeywords: thyroid cancer; tumor immune microenvironment (TIME); immunotherapy; tumor associated macrophages  \n1. Introduction  \nIn the late 19th century, surgeon William Coley noticed that some cancer patients experienced tumor regression after bacterial infections, though the mechanis","cbCaiuau4nKn6Sax","https://ap.wps.com/l/cbCaiuau4nKn6Sax","pdf",1187634,27,"English","# Simple Summary\n# Abstract\n# Keywords\n# 1. Introduction\n## Immune system involvement in cancer\n## Immune checkpoint pathways and ICIs\n## Rationale for focusing on thyroid cancer TIME\n# 2. (Review content continues)","[{\"question\":\"What is the central concept of this review on thyroid cancer therapy?\",\"answer\":\"The review explains how targeting the tumor immune microenvironment (TIME) enables immunotherapies that can work beyond the tumor’s genetic origin, using an agnostic approach.\"},{\"question\":\"Why has immunotherapy progress in thyroid cancer been relatively slow?\",\"answer\":\"Much of the research still concentrates on the genetic landscape of thyroid tumors rather than comprehensive exploration of their TIME and how it shapes immune evasion.\"},{\"question\":\"What components make up the tumor immune microenvironment (TIME) in thyroid cancer?\",\"answer\":\"TIME includes immune cells such as macrophages, lymphocytes, natural killer cells, and mast cells, together with networks of signaling molecules that evolve alongside tumor growth and metastasis.\"}]","Thyroid Cancer - From Potential Drivers to Real Modulators - review | PDF",1790059546,68]