[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-447742-105":59,"doc-detail-447742-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","combination-with-oxaliplatin-improves-abscopal-effect-of-oncolytic-virotherapy-through-reorganization-of-intratumoral-macrophages","Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages","","Intratumoral administration is widely used for oncolytic virotherapy to reach tumor tissue directly and potentially suppress distant untreated lesions via in situ vaccination. The study evaluates oxaliplatin as a way to address limited injectable dose and insufficient distant efficacy. In injected tumors, oxaliplatin improves virus retention by suppressing type I interferons. In distant, virus-naive tumors, it reshapes intratumoral macrophage phenotypes, promoting activated T-cell chemotaxis, recruitment, and inflammation, suggesting a new paradigm for systemic metastases.",{"@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/combination-with-oxaliplatin-improves-abscopal-effect-of-oncolytic-virotherapy-through-reorganization-of-intratumoral-macrophages/447742/",{"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/combination-with-oxaliplatin-improves-abscopal-effect-of-oncolytic-virotherapy-through-reorganization-of-intratumoral-macrophages/447742.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","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},"How does oxaliplatin improve outcomes in virus-injected tumors?","Question",{"text":112,"@type":113},"Oxaliplatin improves virus retention in injected tumors by suppressing type I interferons.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What effect does oxaliplatin have on distant, virus-naive tumors?",{"text":117,"@type":113},"It induces changes in intratumoral macrophage characteristics, leading to chemotaxis and recruitment of activated T cells and an inflammatory state in non-injected tumors.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is improving the abscopal effect important for oncolytic virotherapy?",{"text":121,"@type":113},"Distant tumor efficacy is currently limited, and enhancing in situ vaccination and effector-cell infiltration is needed to prolong patient survival and improve systemic metastasis treatment.","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},447742,1791139973,{"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":145,"preview_page_count":4},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","Original Article  \nCombination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages  \nKyoko Tomita, 1,3 Midori Yamashita, 1,3 Kentaro Ikegami,2 Yoshiko Shimizu, 1 Nobuaki Amino, 1 and Shinsuke Nakao 1  \n1Immuno-Oncology, Astellas Pharma Inc., Tsukuba, Japan; 2DigitalX, ResearchX, Astellas Pharma Inc., Tsukuba, Japan  \nIntratumoral administration is a widely used method for oncolytic virotherapy, as it enables immediate access of virus particles to the target tumor and potentially lead to the suppression of untreated distant tumors via in situ vaccination. However, because the injection volume and concentration of the virus solution are physically limited, the dose level cannot be increased. Additionally, efficacy in distant tumors needs improvement to prolong patient survival. Here, we demonstrate the benefit ofoxaliplatin, with detailed mechanisms revealed through transcriptome analysis, which may provide a solution for the crucial deficiencies of oncolytic virotherapy. In virus-injected tumors, oxaliplatin improved virus retention through suppression of type I interferons. In distant virus-naive tumors, oxaliplatin induced alterations in the intratumoral macrophage characteristics, leading to the chemotaxis and recruitment of activated T cells and subsequently inducing an inflammatory state in the non-injected tumors. Our findings can be a trigger to change the therapeutic paradigm of oncolytic virotherapy for patients with systemic metastases.  \nINTRODUCTION  \nImmune checkpoint inhibitors have made tremendous progress in cancer immunology in this decade.1–3 Anti-programmed cell death- 1/programmed cell death ligand 1 and anti-CTLA4 antibodies have benefitted a subset of patients with solid tumors, demonstrating durable response rates and prolonging survival.4–8 Among cancer immunotherapies, oncolytic virotherapy is a promising option.9–11 Oncolytic viruses are designed to replicate in cancer cells rather than normal cells and therefore directly destroy cancer cells, leading to secretion of damage-and pathogen-associated molecular patterns, as well as tumor antigens, to stimulate antitumor immune responses.12–14 Immune-activating transgenes encoded in the genome of oncolytic viruses further modulate intratumoral immune status and contribute to improved antitumor efficacy,15–17 as clinically proven after treatment with talimogene laherparepvec (T-VEC), which is the first oncolytic virus approved in the United States and carries granulocyte macrophage colony stimulating factor as an immune adjuvant.18–20  \nCurrently, most oncolytic viruses in clinical trials, including T-VEC, are intratumorally administered.11,21,22 Locally injected  \noncolytic viruses are expected to work for in situ vaccination, generating polyclonal T cells against multiple tumor antigens, to achieve regression of both injected and non-injected distant tumors.13,21 This mechanism offers a compelling and distinct approach that sets it apart from other immunotherapies, including immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies, and tumor-antigen targeted antibodies. However, T-VEC, approved in 2015, is the only virus that has been approved in the United States so far. Several reasons account for the lack of additional oncolytic virotherapy approvals besides the regulatory considerations around the use of genetically modified replication-competent viruses in a clinical setting.23 First, efficacy in the injected tumors is limited due to unexpectedly rapid virus exclusion by the host immune defense.24,25 The second is the physically limited amount of virus that can be injected. The third is the limited abscopal effect,26,27 which may be caused by insufficient in situ vaccination in the injected tumors and/or less efficient infiltration of effector cells when distant tumors remain poorly immunogenic. In our prior study, a recombinant oncolytic vaccinia virus carrying interleukin (IL)-7 an","cbCaitCdmPfuR59i","https://ap.wps.com/l/cbCaitCdmPfuR59i","pdf",6965012,14,"English","# Introduction\n## Oncolytic virotherapy and current clinical use\n## Limitations: virus retention and distant (abscopal) efficacy\n## Rationale for oxaliplatin combination","[{\"question\":\"How does oxaliplatin improve outcomes in virus-injected tumors?\",\"answer\":\"Oxaliplatin improves virus retention in injected tumors by suppressing type I interferons.\"},{\"question\":\"What effect does oxaliplatin have on distant, virus-naive tumors?\",\"answer\":\"It induces changes in intratumoral macrophage characteristics, leading to chemotaxis and recruitment of activated T cells and an inflammatory state in non-injected tumors.\"},{\"question\":\"Why is improving the abscopal effect important for oncolytic virotherapy?\",\"answer\":\"Distant tumor efficacy is currently limited, and enhancing in situ vaccination and effector-cell infiltration is needed to prolong patient survival and improve systemic metastasis treatment.\"}]","Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages | PDF",1790722614,35]