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This review examines R848 and R837 as TLR agonists and key immunomodulators in cancer therapy, including their potential roles as monotherapies or combination treatments.",{"@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/new-horizons-in-cancer-immunotherapy-the-evolving-role-of-r848-and-r837-review-review/331539/",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/new-horizons-in-cancer-immunotherapy-the-evolving-role-of-r848-and-r837-review-review/331539.png","ImageObject",300,407,{"name":42,"@type":43},"Quinn","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",15,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the purpose of using immunotherapy in cancer treatment?","Question",{"text":63,"@type":64},"Immunotherapy activates the body’s immune system to defend against cancer cells, offering an approach distinct from chemotherapy and radiotherapy. Clinical trial outcomes can vary by patient and subgroup.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do R848 and R837 function as TLR agonists?",{"text":68,"@type":64},"R848 and R837 are imidazoquinolines that act on TLR7 or TLR8, activating immune cells and promoting Th1 immune responses. They signal through Myd88-dependent pathways to stimulate transcription factors such as NF-κB and JNK.",{"name":70,"@type":61,"acceptedAnswer":71},"What major cytokine effects are associated with R848 and R837?",{"text":72,"@type":64},"Their TLR7/8 signaling leads to production of Th1 cytokines including type I interferon (IFN I), IL-6, IL-12, IFN-γ, and TNF-α. It also suppresses Th2 cytokine IL-4 expression and secretion.","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},331539,1790015126,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},962075114765,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","MOLECULAR AND CLINICAL ONCOLOGY 22: 4, 2025  \nNew horizons in cancer immunotherapy: The evolving role of R848 and R837 (Review)  \nKRUPAR. BHALIYA, MUNEERA ANWER, ALAN MUNN and MING Q. WEI  \nMenzies Health Institute, School of Medical Science, Griffith University, Southport, Queensland 4215, Australia  \nReceived June 4, 2024; Accepted August 7, 2024  \nDOI: 10. 3892/mco.2024.2799  \nAbstract. Therapeutic approaches that increase the efficacy and safety of cancer treatments and improve disease outcomes have been developed worldwide. Immunotherapy uses the body's immune system to inhibit cancerous growth in tissues and organs . Various approaches have been developed to effectively control and inhibit cancerous growth, including checkpoint inhibitors, T‑cell transfer therapy, monoclonal antibodies, vaccines and immunomodulators . Toll‑like receptors (TLRs) target malignant cells by equipping the immune response. In addition, TLR agonists serve a key role in promoting the innate immune system and initiating antigen‑specific T‑cell responses. Notably, TLRs and TLRagonists have been utilized as monotherapies or in combina‑ tion for the treatment of cancer. The present study aimed to review the use of R848 and R837 as TLR agonists, and outline their use as key immunomodulators in cancer therapy.  \nContents  \n1. Introduction  \n2. An overview of R848 and R837  \n3. Mechanisms of action  \n4. Preclinical studies in cancer immunotherapy using R848 and R837  \n5. Clinical trials  \n6. Combination therapy as an advanced therapeutic approach  \n7. Limitations of R837 and R848  \n8. Future directions of the R848 and R837 immunotherapy strategy  \n9. Conclusions  \nCorrespondence to: Ms. Krupa R. Bhaliya, Menzies Health Institute, School of Medical Science, Griffith University, 1 Parklands Drive, Southport, Queensland 4215, Australia  \nE‑[mail: krupa.bhaliya@griffithuni.edu.au](mail: krupa.bhaliya@griffithuni.edu.au)  \nKey words: immunomodulation, adjuvant, cancer immunotherapy, Toll‑like receptors  \n1. Introduction  \nImmunotherapy utilizes the body's immune system to act as a natural defense against cancer cells, which is notably different to traditional cancer treatments, including chemotherapy and radiotherapy. Advancements in immunotherapy have revolu‑ tionized disease management and cancer immunology. Results of clinical trials demonstrated that several types of immu‑ notherapies, such as adoptive cellular therapy and immune checkpoint inhibitors (ICIs), exhibit potential in the treatment of cancer; however, efficacy may vary between patients and benefits may only be observed in certain groups (1) .  \nReceptors, such as Toll‑like receptors (TLRs), bridge the gap between innate and adaptive immunity, highlighting them as potential targets for therapeutic interventions. TLRs contribute to the first line of defense against pathogens, triggering signaling pathways that initiate immune and inflam‑ matory responses (2) .  \nThe limited immunogenicity of cancer cells in combi‑ nation with an immunosuppressive microenvironment is a pivotal protective factor that allows evasion of immune surveillance. Immune cells do not distinctly recognize tumor cells, and the tumor microenvironment (TME) notably hinders the infiltration or survival of immune cells (3) .  \nTLRs are evolutionarily‑conserved receptors that play a vital role in immune responses, particularly in recognizing microbes. TLRs belong to the family of pattern recognition receptors and are directly involved in regulating inflammatory responses, as well as activating innate or adaptive immune responses to eliminate infectious microorganisms and debris derived from cancer cells.  \nTLRs expressed on the cell membrane form an effective group with those located on the endosomal plasma membrane. These include TLR1, TLR2, TLR4, TLR5, TLR6, TLR10, TLR3, TLR7, TLR8 and TLR9 . In cancer immunotherapy, the modulation of TLRs is employed to enhance the immune response against cancer cells. Thus, specific drugs o","cbCaifvXP3pHkIKp","https://ap.wps.com/l/cbCaifvXP3pHkIKp","pdf",2101162,14,"English","# Introduction\n## Overview of TLRs and immunotherapy rationale\n# An overview of R848 and R837\n## R848 (Resiquimod): targets and effects\n## R837 (Imiquimod): targets and established combinations\n# Mechanisms of action\n## TLR7/8 signaling and Th1 cytokine induction","[{\"question\":\"What is the purpose of using immunotherapy in cancer treatment?\",\"answer\":\"Immunotherapy activates the body’s immune system to defend against cancer cells, offering an approach distinct from chemotherapy and radiotherapy. Clinical trial outcomes can vary by patient and subgroup.\"},{\"question\":\"How do R848 and R837 function as TLR agonists?\",\"answer\":\"R848 and R837 are imidazoquinolines that act on TLR7 or TLR8, activating immune cells and promoting Th1 immune responses. They signal through Myd88-dependent pathways to stimulate transcription factors such as NF-κB and JNK.\"},{\"question\":\"What major cytokine effects are associated with R848 and R837?\",\"answer\":\"Their TLR7/8 signaling leads to production of Th1 cytokines including type I interferon (IFN I), IL-6, IL-12, IFN-γ, and TNF-α. It also suppresses Th2 cytokine IL-4 expression and secretion.\"}]","New horizons in cancer immunotherapy: The evolving role of R848 and R837 (Review) - Review | PDF",1789993803,35]