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In a phase-I trial, one patient showed a 313-day prolonged response after combined oncolytic virotherapy and anti-PD-L1 treatment. Multi-omics profiling of this responder and three nonresponders mapped a shift in the tumor microenvironment: initially low T- and NK-cell infiltration with relatively more macrophages, followed by progressive increases of CD4+ T cells, CD8+ T cells, and B cells during therapy. These changes coincided with enhanced transcription factors linked to T-cell activation and cytotoxicity, and peripheral blood monitoring revealed a rapid decline in ctDNA, supporting its potential as an early biomarker. Overall, the study links virotherapy-induced remodeling of a “cold” TME to improved immunotherapy sensitivity.",{"@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/the-long-term-effectiveness-and-mechanism-of-oncolytic-virotherapy-combined-with-anti-pd-l1-antibody-in-colorectal-cancer-patient/341866/",{"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/the-long-term-effectiveness-and-mechanism-of-oncolytic-virotherapy-combined-with-anti-pd-l1-antibody-in-colorectal-cancer-patient/341866.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","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 was the key long-term clinical observation in the phase-I trial?","Question",{"text":112,"@type":113},"One patient achieved a 313-day prolonged response during combined oncolytic virotherapy and immunotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What immune changes were observed in the responder’s tumor tissue during treatment?",{"text":117,"@type":113},"CD4+ T cells, CD8+ T cells, and B cells progressively increased, alongside upregulation of T-cell activation and cytotoxicity transcription factors.",{"name":119,"@type":110,"acceptedAnswer":120},"How did circulating tumor DNA (ctDNA) behave, and why is it important?",{"text":121,"@type":113},"Peripheral blood monitoring showed a rapid decrease in ctDNA, suggesting it could serve as an early blood biomarker of treatment efficacy.","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},341866,1790523290,{"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},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","[www.nature.com/cgt](www.nature.com/cgt) Cancer Gene Therapy  \nARTICLE OPEN   \nThe long-term effectiveness and mechanism of oncolytic virotherapy combined with anti-PD-L1 antibody in colorectal cancer patient  \nHangyu Zhang 1,6, Yiqing Ren 1,6, Feiyu Wang2,6, Xiaoxuan Tu1, Zhou Tong1, Lulu Liu1, Yi Zheng 1, Peng Zhao 1, Jinlin Cheng3, Jianwen Li 4 ✉, Weijia Fang 1 ✉ and Xia Liu 5 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | Colorectal cancer (CRC) is known to be resistant to immunotherapy. In our phase-I clinical trial, one patient achieved a 313-day prolonged response during the combined treatment of oncolytic virotherapy and immunotherapy. To gain a deeper understanding of the potential molecular mechanisms, we performed a comprehensive multi-omics analysis on this patient and three nonresponders. Our investigation unveiled that, initially, the tumor microenvironment (TME) of this responder presented minimal infiltration of T cells and natural killer cells, along with a relatively higher presence of macrophages compared to non-responders. Remarkably, during treatment, there was a progressive increase in CD4+ T cells, CD8+ T cells, and B cells in the responder’s tumor tissue. This was accompanied by a significant upregulation of transcription factors associated with T-cell activation and cytotoxicity, including GATA3, EOMES, and RUNX3 . Furthermore, dynamic monitoring of peripheral blood samples from the responder revealed a rapid decrease in circulating tumor DNA (ctDNA), suggesting its potential as an early blood biomarker of treatment efficacy. Collectively, our findings demonstrate the effectiveness of combined oncolytic virotherapy and immunotherapy in certain CRC patients and provide molecular evidence that virotherapy can potentially transform a “cold” TME into a “hot” one, thereby |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| improving sensitivity to immunotherapy. |  |  |\n|  | Cancer Gene Therapy (2024) 31:1412–1426; [https://doi.org/10.1038/s41417-024-00807-2](https://doi.org/10.1038/s41417-024-00807-2) |  |\n|  |  |  |\n\nINTRODUCTION  \nColorectal cancer (CRC) stands as the third leading cause of global cancer-related mortality [1], and its incidence is higher in people related to obesity, physical inactivity, or alcohol consumption and is increasing in younger patients (≤50 years) [2] . Approximately 20% of newly diagnosed CRC have synchronous metastasis, and the liver turns out to be the most common metastasis organ [3] . Colorectal liver metastasis has a poor prognosis, and the phenotype of more than 95% metastasis CRC (mCRC) is microsatellite stable (MSS) [4] . It is reported that only 20–30% CRLM patients have the opportunity of surgery [5], while the rest are mainly treated with systemic chemotherapy and often show primary resistance to immunotherapy due to the presence of an immunosuppressive microenvironment associated with MSS status and the deletion of CD8+T cells mechanisms co-opted by liver metastases to manipulate host peripheral tolerance [6] .  \nOncolytic viruses (OVs) exhibit the properties of selective infection, replication, and targeted propagation within tumors [7] . They have the unique ability to preferentially target and eliminate cancer cells, often mediated through dendritic cells [8] . The process of oncolysis also leads to the release of tumor-  \nassociated antigens (TAAs) and heightened cytokine expression, recognized as potential mechanisms to enhance the therapeutic effectiveness of immune checkpoint blockade (ICB) in malignancies that typically exhibit poor response rates [9, 10] . Indeed, the combination of OVs with anti-PD-1 therapy has demonstrated both safety and a potent therapeutic response in melanoma patients [11] . Preclinical studies have demonstrated promising antitumor effects of oncolytic viruses in CRC [12–14] . In CRC patients, Garcia-Carbonero et al. found a noteworthy occurren","cbCaianGB3gNDug1","https://ap.wps.com/l/cbCaianGB3gNDug1","pdf",3206216,15,"English","# Introduction\n## Colorectal cancer resistance and clinical context\n## Rationale for oncolytic viruses and immune checkpoint blockade\n## Engineered oncolytic herpesvirus (OH2) and design logic","[{\"question\":\"What was the key long-term clinical observation in the phase-I trial?\",\"answer\":\"One patient achieved a 313-day prolonged response during combined oncolytic virotherapy and immunotherapy.\"},{\"question\":\"What immune changes were observed in the responder’s tumor tissue during treatment?\",\"answer\":\"CD4+ T cells, CD8+ T cells, and B cells progressively increased, alongside upregulation of T-cell activation and cytotoxicity transcription factors.\"},{\"question\":\"How did circulating tumor DNA (ctDNA) behave, and why is it important?\",\"answer\":\"Peripheral blood monitoring showed a rapid decrease in ctDNA, suggesting it could serve as an early blood biomarker of treatment efficacy.\"}]","The long-term effectiveness and mechanism of oncolytic virotherapy combined with anti-PD-L1 antibody in colorectal cancer patient | PDF",1790044202,38]