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The text explains why intact antiviral interferon pathways can neutralize oncolytic viruses, while arenaviruses evade immunity through mechanisms such as MAVS-dependent IFN pathway inhibition and spike antigen masking. It highlights how LCMV can generate long-term tumor microenvironment responses, enhance anti-tumor immunity, and polarize cold tumors toward a hot phenotype. It also covers preclinical and clinical applications and vector-based vaccine approaches using attenuated replicating arenaviruses.",{"@graph":69,"@context":123},[70,84,106],{"@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/arenaviruses-old-viruses-present-new-solutions-for-cancer-therapy/385674/",{"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/arenaviruses-old-viruses-present-new-solutions-for-cancer-therapy/385674.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are arenaviruses considered promising for cancer therapy in cold tumors?","Question",{"text":113,"@type":114},"The review links cold tumors to poor immune cell infiltration and ineffective innate responses. Arenaviruses, especially LCMV, can evade immune clearance and help convert poorly infiltrated tumors toward a more immunogenic “hot” phenotype.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does LCMV avoid neutralization by the host immune system?",{"text":118,"@type":114},"The text attributes immune escape to inhibition of the MAVS-dependent IFN pathway and spike protein antigen masking, which supports longer persistence and therapeutic impact in the tumor microenvironment.",{"name":120,"@type":111,"acceptedAnswer":121},"What types of clinical or translational applications does the review highlight?",{"text":122,"@type":114},"It focuses on noncytopathic arenavirus anti-cancer approaches and also notes current use of LCMV and Pichinde arenaviruses to create vector-based vaccines using attenuated but replicating virus.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},385674,1790342624,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","TYPE Review  \nPUBLISHED 24 March 2023  \nDOI 10.3389/fimmu.2023.1110522  \nOPEN ACCESS  \nEDITED BY  \nJayakumar Nair,  \nNational Institutes of Health (NIH), United States  \nREVIEWED BY  \nToshana Foster,  \nUniversity of Nottingham, United Kingdom Peter James Mullen,  \nUniversity of Southern California, United States  \n*CORRESPONDENCE Aleksandra A. Pandyra  \n [aleksandra.pandyra@uni-duesseldorf.de](aleksandra.pandyra@uni-duesseldorf.de)  \nSPECIALTY SECTION  \nThis article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology  \nRECEIVED 28 November 2022  \nACCEPTED 13 March 2023  \nPUBLISHED 24 March 2023  \nCITATION  \nStachura P, Stencel O, Lu Z, Borkhardt A and Pandyra AA (2023) Arenaviruses:  \nOld viruses present new solutions for cancer therapy.  \nFront. Immunol. 14:1110522 .  \ndoi: 10.3389/fimmu.2023.1110522  \nCOPYRIGHT  \n© 2023 Stachura, Stencel, Lu, Borkhardt and Pandyra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nArenaviruses: Old viruses present new solutions for cancer therapy  \nPaweł Stachura 1,2, Olivia Stencel 1, Zhe Lu 1, Arndt Borkhardt 1 and Aleksandra A. Pandyra 1*  \n1 Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, HeinrichHeine-University, Düsseldorf, Germany, 2 Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany  \nViral-based cancer therapies have tremendous potential, especially in the context of treating poorly infiltrated cold tumors. However, in tumors with intact anti-viral interferon (IFN) pathways, while some oncolytic viruses induce strong innate and adaptive immune responses, they are neutralized before exerting their therapeutic effect. Arenaviruses, particularly the lymphocytic choriomeningitis virus (LCMV) is a noncytopathic virus with preferential cancer tropism and evolutionary mechanisms to escape the immune system for longer and to block early clearance. These escape mechanisms include inhibition of the MAVS dependent IFN pathway and spike protein antigen masking. Regarding its potential for cancer treatment, LCMV is therefore able to elicit long-term responses within the tumor microenvironment (TME), boost anti-tumor immune responses and polarize poorly infiltrating tumors towards a hot phenotype. Other arenaviruses including the attenuated Junin virus vaccine also have anti-tumor effects . Furthermore, the LCMV and Pichinde arenaviruses are currently being used to create vector-based vaccines with attenuated but replicating virus . This review focuses on highlighting the potential of arenaviruses as anti-cancer therapies. This includes providing a molecular understanding of its tropism as well as highlighting past and present preclinical and clinical applications of noncytophatic arenavirus therapies and their potential in bridging the gap in the treatment of cancers weakly responsive or unresponsive to oncolytic viruses. In summary, arenaviruses represent promising new therapies to broaden the arsenal of anti-tumor therapies for generating an immunogenic tumor microenvironment  \nKEYWORDS  \nvirotherapy, arenaviruses, LCMV (lymphocytic choriomeningitis virus), immunomodualtors, cold tumors, noncytopathic virus  \nIntroduction  \nRecognition of the importance of the immune system in tumor surveillance has revolutionized the therapeutic landscape with the advent of immunotherapies such as checkpoint inhibitors (CI) (1) . Despite some breakthroughs, tumor immune evasion provides obstacles to effective CI and/or other immunotherapeutic treatments focused  \nFrontiers in Immun","cbCaiqXiFFtWnkPA","https://ap.wps.com/l/cbCaiqXiFFtWnkPA","pdf",1394555,11,"English","# Introduction\n## Viral-based cancer therapies and immune evasion in the tumor microenvironment\n# Arenaviruses as noncytopathic anti-cancer agents\n## Immune escape mechanisms and effects on tumor microenvironment phenotypes\n## Preclinical and clinical applications and vaccine vector platforms","[{\"question\":\"Why are arenaviruses considered promising for cancer therapy in cold tumors?\",\"answer\":\"The review links cold tumors to poor immune cell infiltration and ineffective innate responses. Arenaviruses, especially LCMV, can evade immune clearance and help convert poorly infiltrated tumors toward a more immunogenic “hot” phenotype.\"},{\"question\":\"How does LCMV avoid neutralization by the host immune system?\",\"answer\":\"The text attributes immune escape to inhibition of the MAVS-dependent IFN pathway and spike protein antigen masking, which supports longer persistence and therapeutic impact in the tumor microenvironment.\"},{\"question\":\"What types of clinical or translational applications does the review highlight?\",\"answer\":\"It focuses on noncytopathic arenavirus anti-cancer approaches and also notes current use of LCMV and Pichinde arenaviruses to create vector-based vaccines using attenuated but replicating virus.\"}]","Arenaviruses: Old viruses present new solutions for cancer therapy | PDF",1790270523,28]