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Antigen processing and presentation remain largely untargeted despite being central to immune response development. This study hypothesizes that tumor-driven cytokine alterations disrupt antigen presentation and that normalization via locoregional cytokine delivery or targeted immunological adjuvant delivery can improve immunotherapy outcomes.",{"@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/overcoming-impaired-antigen-presentation-in-tumor-draining-lymph-nodes-facilitates-immunotherapy-research-article/434947/",{"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/overcoming-impaired-antigen-presentation-in-tumor-draining-lymph-nodes-facilitates-immunotherapy-research-article/434947.png","ImageObject",300,407,{"name":92,"@type":93},"Dipper","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does this study address in immunotherapy?","Question",{"text":112,"@type":113},"Approved immunotherapies often fail because they mainly target specific steps, while antigen processing and presentation are rarely addressed. The study focuses on impairments in antigen presentation within tumor-draining lymph nodes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What do the authors find about dendritic cell antigen presentation?",{"text":117,"@type":113},"Breast tumors induce local impairments in dendritic cell antigen presentation that limit antigen-specific T cell responses. Antigen processing in dendritic cells within tumor-draining lymph nodes is not impaired.",{"name":119,"@type":110,"acceptedAnswer":120},"How can the impairments be overcome?",{"text":121,"@type":113},"The study links the impairment to reduced IL-1β in tumor-draining lymph nodes. It shows improved anti-tumor T cell responses using an antigen-agnostic immunological adjuvant delivery strategy to distant, cancer-antigen-positive lymph nodes, and also recovery by exogenous IL-1β delivery, especially when combined with immune checkpoint blockade.","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},434947,1791006163,{"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":29,"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":36,"preview_page_count":4},1374404997633,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Open access Original research  \nTo cite: O’Melia MJ, Menzel L, Lei P-J, et al. Overcoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy. Journal for ImmunoTherapy of Cancer 2025;13:e013364 . doi:10.1136/jitc-2025-013364  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2025-013364](jitc-2025-013364)) .  \nAccepted 15 December 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Meghan J. O’Melia; [momelia@mgh.harvard.edu](momelia@mgh.harvard.edu)  \nDr Lance L Munn;  \n[lmunn@mgh.harvard.edu](lmunn@mgh.harvard.edu)  \nProfessor Timothy P Padera; [tpadera@mgh.harvard.edu](tpadera@mgh.harvard.edu)  \nOvercoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy  \nMeghan J. O’Melia  ,1 Lutz Menzel,1 Pin-Ji Lei  ,1 Hengbo Zhou,1  \nXingjian Zhang,1 Neian Contreras-Alvarado,1,2 Johanna J Rajotte,1 Lingshan Liu,1 Mohammad R Nikmaneshi,1 James W Baish,3 Jessalyn M Ubellacker,4 Genevieve M Boland,5 Sonia Cohen,5 Timothy P Padera,1 Lance L Munn1  \nABSTRACT  \nBackground Immunotherapies have revolutionized cancer care in recent decades, but approved therapies often fail and currently only target specific steps in the generation of anti-cancer immune responses. Notably, the majority of approved immunotherapies do not target antigen processing and presentation, which are key steps in the development of immune responses and harbor potential as targets to improve immunotherapy. Here, we hypothesize that tumor-mediated alterations in cytokine concentrations alter antigen presentation, which can be normalized by locoregional cytokine delivery or targeted immunological adjuvant delivery.  \nMethods We used mouse models of breast cancer, with analysis by flow cytometry, immunofluorescence, confocal imaging, and single-cell RNA sequencing to address the impacts of tumors on locoregional antigen presentation, along with mechanisms to remedy these impacts.  \nResults Here, we demonstrate that breast tumors induce locoregional impairments in dendritic cell antigen presentation that limits anti-cancer antigenspecific T cell responses. Antigen processing was not impaired in dendritic cells within the tumor-draining lymph node. A reduction of the cytokine IL-1β in tumordraining lymph nodes was responsible for impairmentsin antigen presentation by dendritic cells. As such, we tested the ability of dendritic cells in lymph nodes at various distances from the primary tumor to be activated utilizing an antigen-agnostic immunological adjuvant delivery strategy. We observed improved antitumor T cell responses when immunological adjuvant was delivered to cancer antigen-positive lymph nodes distant from the tumor, suggesting that these lymph nodes can be targeted to improve anti-cancer immune responses. When combined with immune checkpoint blockade, delivery of immunological adjuvant to distant lymph nodes led to long-term survival and protection from recurrence. Antigen presentation by dendritic cells and T cell responses could also be recovered by exogenous delivery of IL-1β via intratumoral injection, with improved survival when combined with immune checkpoint blockade.  \nConclusions This study demonstrates that tumor-induced impairments in antigen presentation in tumor-draining lymph nodes can be overcome by the appropriate introduction of immunological adjuvant to tumor-distant lymph nodes or by restoring IL-1β to the tumor-draining  \nWHAT IS ALREADY KNOWN ON THIS TOPIC  \n\n| ⇒ Tumor-induced suppression can impair the ability of the immune system to mount an efficient and lasting immune response against the tumors.\u003Cbr>WHAT THIS STUDY ADDS |\n| --- |\n| ⇒ Breast tumors induce local ","cbCairKelDr5lB0T","https://ap.wps.com/l/cbCairKelDr5lB0T","pdf",974291,16,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# What is already known on this topic\n# What this study adds\n# How this study might affect research, practice or policy\n# Introduction","[{\"question\":\"What problem does this study address in immunotherapy?\",\"answer\":\"Approved immunotherapies often fail because they mainly target specific steps, while antigen processing and presentation are rarely addressed. The study focuses on impairments in antigen presentation within tumor-draining lymph nodes.\"},{\"question\":\"What do the authors find about dendritic cell antigen presentation?\",\"answer\":\"Breast tumors induce local impairments in dendritic cell antigen presentation that limit antigen-specific T cell responses. Antigen processing in dendritic cells within tumor-draining lymph nodes is not impaired.\"},{\"question\":\"How can the impairments be overcome?\",\"answer\":\"The study links the impairment to reduced IL-1β in tumor-draining lymph nodes. It shows improved anti-tumor T cell responses using an antigen-agnostic immunological adjuvant delivery strategy to distant, cancer-antigen-positive lymph nodes, and also recovery by exogenous IL-1β delivery, especially when combined with immune checkpoint blockade.\"}]","Overcoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy - Research article | PDF",1790671240]