[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-340288-105":59,"doc-detail-340288-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","cold-and-hot-tumors-from-molecular-mechanisms-to-targeted-therapy","Cold and hot tumors: from molecular mechanisms to targeted therapy","","Cold and hot tumors describe contrasting immune landscapes that influence response to immune checkpoint blockade (ICB) in solid cancers. Only a subset of patients benefits, typically those with an immune-inflamed “hot” phenotype characterized by robust cytotoxic T-cell infiltration and related microenvironment features. Non-responsive cases often show an immune-desert “cold” phenotype, with an intermediate “excluded” type. This review explains key molecular and microenvironmental determinants, clarifies tumor-intrinsic and external regulators, and summarizes strategies and drug targets to convert cold or altered tumors into hot states to improve clinical efficacy.",{"@graph":69,"@context":122},[70,84,105],{"@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/cold-and-hot-tumors-from-molecular-mechanisms-to-targeted-therapy/340288/",{"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/cold-and-hot-tumors-from-molecular-mechanisms-to-targeted-therapy/340288.png","ImageObject",300,407,{"name":92,"@type":93},"Skyler","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What immune phenotypes distinguish “hot” and “cold” tumors in ICB therapy?","Question",{"text":112,"@type":113},"“Hot” tumors show an immune-inflamed profile with active immune activity in the tumor microenvironment, making them more responsive to immune checkpoint inhibitors. “Cold” tumors are associated with a lack of effective immune activity and can be less responsive.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the “excluded” immune phenotype and how does it relate to cold and hot tumors?",{"text":117,"@type":113},"The immune “excluded” phenotype lies between the cold and hot categories. It represents a more nuanced immune state that can affect how immune cells access and function in the tumor tissue.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are combination therapies often needed for cold or altered tumors?",{"text":121,"@type":113},"Because ICB therapy has limited efficacy against cold or altered tumors, combinations are used to enhance immune cell infiltration into tumor tissue and to promote conversion toward a hot-like immune state.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},340288,1790139303,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"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":145},2336464648746,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","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  \nCold and hot tumors: from molecular mechanisms to targeted therapy  \nBo Wu1, Bo Zhang2, Bowen Li3, Haoqi Wu4 and Meixi Jiang 1 ✉  \n\n|  | Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which has shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment in cancer therapy, only a minority of patients exhibit a positive response to it. In patients with solid tumors, those who respond well to ICB treatment typically demonstrate an active immune profile referred to as the “hot” (immune-inflamed) phenotype. On the other hand, non-responsive patients may exhibit a distinct “cold”(immune-desert) phenotype, differing from the features of “hot” tumors. Additionally, there is a more nuanced “excluded” immune phenotype, positioned between the “cold” and “hot” categories, known as the immune “excluded” type. Effective differentiation between “cold” and “hot” tumors, and understanding tumor intrinsic factors, immune characteristics, TME, and external factors are critical for predicting tumor response and treatment results. It is widely accepted that ICB therapy exerts a more profound effect on “hot” tumors, with limited efficacy against “cold” or “altered”tumors, necessitating combinations with other therapeutic modalities to enhance immune cell infiltration into tumor tissue and convert “cold” or “altered” tumors into “hot” ones. Therefore, aligning with the traits of “cold” and “hot” tumors, this review systematically delineates the respective immune characteristics, influencing factors, and extensively discusses varied treatment |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| approaches and drug targets based on “cold” and “hot” tumors to assess clinical efficacy. |  |  |\n|  | Signal Transduction and Targeted Therapy (2024)9:274 ; [https://doi.org/10.1038/s41392-024-01979-x](https://doi.org/10.1038/s41392-024-01979-x) |  |\n|  |  |  |\n\nINTRODUCTION  \nImmunotherapy aims to restore the innate antitumor immune response, revitalizing and maintaining the tumor-specific immune pathway.1–5 The development and clinical application of ICB therapies for various cancers have shown promising results.6,7 The efficacy of immunotherapy can vary among patients with the same cancer type, possibly due to the immune characteristics of the tumor.8,9 As a result, the concept of “cold-hot” tumor immune phenotypes has been proposed to characterize the immune status of tumors and predict the anticipated response to ICB therapy based on the type, quantity, and distribution of immune cell infiltration in the tumor microenvironment.10 This classification provides valuable insights for overcoming the shortcomings of initial treatment strategies.11  \nThe complexity of the tumor microenvironment (TME) arises from the intricate interactions between tumor cells and various factors within the TME, involving both promoting and inhibitory mechanisms.12 Immune cells play a crucial role within the TME, with CD8+ T cells serving as pivotal participants in the immune response against tumors, effectively executing immune surveillance.13 Structurally, components such as tertiary lymphoid structures and the tumor stroma not only provide support for cellular activities but also play a significant role in shaping the TME.14, 15 Moreover, the activities of tumor cells and immune cells are not independent but regulated by intrinsic factors such as epigenetic modifications and signaling pathways of the innate immune system.16, 17 Both tumor cells and immune cells respond  \nto external factors through metabolism, controlling tumor immune characteristics through metabolite-driven gene expression a","cbCainATMeOcj34Z","https://ap.wps.com/l/cbCainATMeOcj34Z","pdf",5353910,65,"English","# Introduction\n# Tumor microenvironment and immune phenotypes\n# Immune “hot”, “cold”, and “excluded” states\n# Implications for ICB response and treatment design\n# Therapeutic approaches and drug targets","[{\"question\":\"What immune phenotypes distinguish “hot” and “cold” tumors in ICB therapy?\",\"answer\":\"“Hot” tumors show an immune-inflamed profile with active immune activity in the tumor microenvironment, making them more responsive to immune checkpoint inhibitors. “Cold” tumors are associated with a lack of effective immune activity and can be less responsive.\"},{\"question\":\"What is the “excluded” immune phenotype and how does it relate to cold and hot tumors?\",\"answer\":\"The immune “excluded” phenotype lies between the cold and hot categories. It represents a more nuanced immune state that can affect how immune cells access and function in the tumor tissue.\"},{\"question\":\"Why are combination therapies often needed for cold or altered tumors?\",\"answer\":\"Because ICB therapy has limited efficacy against cold or altered tumors, combinations are used to enhance immune cell infiltration into tumor tissue and to promote conversion toward a hot-like immune state.\"}]","Cold and hot tumors: from molecular mechanisms to targeted therapy | PDF",1790035549,164]