{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:50:56Z","timestamp":1792612256400,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972308"],"award-info":[{"award-number":["81972308"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Given malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single\u2010cell RNA sequencing. Furthermore, anti\u2010interleukin (IL)\u20106R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL\u20106 hypersecretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OH2 was able to eliminate ascites and significantly prolong the survival of mice\u2010bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro\u2010inflammatory cytokines, mainly IL\u20106, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5\u2010fluorouracil or nonresponders. Furthermore, the initial\u2010stage blocking of the IL\u20106 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single\u2010cell RNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>OH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL\u20106, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4772","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T07:21:50Z","timestamp":1651735310000},"page":"4297-4309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A novel oncolytic virus induces a regional cytokine storm and safely eliminates malignant ascites of colon cancer"],"prefix":"10.1002","volume":"11","author":[{"given":"Shuang","family":"Dong","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Department of Oncology, Hubei Cancer Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binlei","family":"Liu","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology Hubei University of Technology  Wuhan Hubei 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