{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:28:01Z","timestamp":1787041681667,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1038\/s41401-026-01829-2","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:02:05Z","timestamp":1779674525000},"page":"2668-2681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sirolimus potentiates oncolytic Virus M1 efficacy through tumor-selective augmentation of viral replication"],"prefix":"10.1038","volume":"47","author":[{"given":"Jie-hong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-xin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan-ming","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-hua","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-kai","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-mei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-bo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"1829_CR1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","volume":"20","author":"SZ Shalhout","year":"2023","unstructured":"Shalhout SZ, Miller DM, Emerick KS, Kaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20:160\u201377.","journal-title":"Nat Rev Clin Oncol"},{"key":"1829_CR2","doi-asserted-by":"publisher","first-page":"E4504","DOI":"10.1073\/pnas.1408759111","volume":"111","author":"Y Lin","year":"2014","unstructured":"Lin Y, Zhang H, Liang J, Li K, Zhu W, Fu L, et al. Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers. Proc Natl Acad Sci USA. 2014;111:E4504\u201312.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1829_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03285-0","volume":"11","author":"Y Liu","year":"2020","unstructured":"Liu Y, Cai J, Liu W, Lin Y, Guo L, Liu X, et al. Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade. Cell Death Dis. 2020;11:1062.","journal-title":"Cell Death Dis"},{"key":"1829_CR4","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1002\/ijc.33703","volume":"149","author":"W Liu","year":"2021","unstructured":"Liu W, Liu Y, Hu C, Xu C, Chen J, Chen Y, et al. Cytotoxic T lymphocyte-associated protein 4 antibody aggrandizes antitumor immune response of oncolytic virus M1 via targeting regulatory T cells. Int J Cancer. 2021;149:1369\u201384.","journal-title":"Int J Cancer"},{"key":"1829_CR5","doi-asserted-by":"crossref","unstructured":"Liu Y, Xu C, Xiao X, Chen Y, Wang X, Liu W, et al. Overcoming resistance to oncolytic virus M1 by targeting PI3K-gamma in tumor-associated myeloid cells. Mol Ther. 2022;30:3677\u201393.","DOI":"10.1016\/j.ymthe.2022.05.008"},{"key":"1829_CR6","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1158\/1078-0432.CCR-25-1620","volume":"31","author":"C Xie","year":"2025","unstructured":"Xie C, Zheng X, He S, Xu W, Zhu W, Yan G, et al. Clinical evaluation of M1-c6v1 oncolytic virus combined with camrelizumab and apatinib in advanced hepatocellular carcinoma. Clin Cancer Res. 2025;31:4288\u201398.","journal-title":"Clin Cancer Res"},{"key":"1829_CR7","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.gendis.2021.03.002","volume":"9","author":"L Chen","year":"2022","unstructured":"Chen L, Song M, Yao C. Calcineurin in development and disease. Genes Dis. 2022;9:915\u201327.","journal-title":"Genes Dis"},{"key":"1829_CR8","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","volume":"8","author":"V Panwar","year":"2023","unstructured":"Panwar V, Singh A, Bhatt M, Tonk RK, Azizov S, Raza AS, et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct Target Ther. 2023;8:375.","journal-title":"Signal Transduct Target Ther"},{"key":"1829_CR9","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/jnci\/djj161","volume":"98","author":"H Ito","year":"2006","unstructured":"Ito H, Aoki H, K\u00fchnel F, Kondo Y, Kubicka S, Wirth T, et al. Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus. J Natl Cancer Inst. 2006;98:625\u201336.","journal-title":"J Natl Cancer Inst"},{"key":"1829_CR10","doi-asserted-by":"publisher","first-page":"4720","DOI":"10.1128\/JVI.02032-10","volume":"85","author":"H Jiang","year":"2011","unstructured":"Jiang H, White EJ, R\u00edos-Vicil CI, Xu J, Gomez-Manzano C, Fueyo J. Human adenovirus type 5 induces cell lysis through autophagy and autophagy-triggered caspase activity. J Virol. 2011;85:4720\u20139.","journal-title":"J Virol"},{"key":"1829_CR11","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/neuonc\/nop056","volume":"12","author":"LT Yu","year":"2010","unstructured":"Yu LT, Baxter PA, Voicu H, Gurusiddappa S, Zhao YJ, Adesina A, et al. A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo. Neuro Oncol. 2010;12:580\u201394.","journal-title":"Neuro Oncol"},{"key":"1829_CR12","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1089\/hum.2020.273","volume":"32","author":"W Zhu","year":"2021","unstructured":"Zhu W, Liang J, Tan J, Guo L, Cai J, Hu J, et al. Real-time visualization and quantification of oncolytic M1 virus in vitro and in vivo. Hum Gene Ther. 2021;32:158\u201365.","journal-title":"Hum Gene Ther"},{"key":"1829_CR13","doi-asserted-by":"crossref","unstructured":"Liang X, Li J, Chen J, Chen C, Li H, Yan C, et al. TAMs-mediated resistance to oncolytic virus M1 in solid tumors. J Immunother Cancer. 2025;13:e012858.","DOI":"10.1136\/jitc-2025-012858"},{"key":"1829_CR14","doi-asserted-by":"publisher","first-page":"3677","DOI":"10.1016\/j.ymthe.2022.05.008","volume":"30","author":"Y Liu","year":"2022","unstructured":"Liu Y, Xu C, Xiao X, Chen Y, Wang X, Liu W, et al. Overcoming resistance to oncolytic virus M1 by targeting PI3K-\u03b3 in tumor-associated myeloid cells. Mol Ther. 2022;30:3677\u201393.","journal-title":"Mol Ther"},{"key":"1829_CR15","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1158\/1078-0432.CCR-18-3626","volume":"26","author":"B Tang","year":"2020","unstructured":"Tang B, Guo ZS, Bartlett DL, Yan DZ, Schane CP, Thomas DL, et al. Synergistic combination of oncolytic virotherapy and immunotherapy for glioma. Clin Cancer Res. 2020;26:2216\u201330.","journal-title":"Clin Cancer Res"},{"key":"1829_CR16","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1089\/hum.2017.041","volume":"28","author":"S Yuan","year":"2017","unstructured":"Yuan S, Wu Y, Wang Y, Chen J, Chu L. An oncolytic adenovirus expressing snord44 and gas5 exhibits antitumor effect in colorectal cancer cells. Hum Gene Ther. 2017;28:690\u2013700.","journal-title":"Hum Gene Ther"},{"key":"1829_CR17","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1182\/blood-2014-01-553362","volume":"124","author":"I Ricciardelli","year":"2014","unstructured":"Ricciardelli I, Blundell MP, Brewin J, Thrasher A, Pule M, Amrolia PJ. Towards gene therapy for EBV-associated posttransplant lymphoma with genetically modified EBV-specific cytotoxic T cells. Blood. 2014;124:2514\u201322.","journal-title":"Blood"},{"key":"1829_CR18","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/sj.cgt.7700949","volume":"13","author":"N Smakman","year":"2006","unstructured":"Smakman N, van der Bilt JD, van den Wollenberg DJ, Hoeben RC, Borel Rinkes IH, Kranenburg O. Immunosuppression promotes reovirus therapy of colorectal liver metastases. Cancer Gene Ther. 2006;13:815\u20138.","journal-title":"Cancer Gene Ther"},{"key":"1829_CR19","doi-asserted-by":"publisher","first-page":"11206","DOI":"10.18632\/oncotarget.14493","volume":"8","author":"S Tai","year":"2017","unstructured":"Tai S, Xu L, Xu M, Zhang L, Zhang Y, Zhang K, et al. Combination of arsenic trioxide and everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells. Oncotarget. 2017;8:11206\u201318.","journal-title":"Oncotarget"},{"key":"1829_CR20","doi-asserted-by":"crossref","unstructured":"Gujar S, Pol JG, Kim Y, Lee PW, Kroemer G. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies. Trends Immunol. 2018;39:209\u201321.","DOI":"10.1016\/j.it.2017.11.006"},{"key":"1829_CR21","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41417-018-0011-8","volume":"25","author":"C Comins","year":"2018","unstructured":"Comins C, Simpson GR, Rogers W, Relph K, Harrington K, Melcher A, et al. Synergistic antitumour effects of rapamycin and oncolytic reovirus. Cancer Gene Ther. 2018;25:148\u201360.","journal-title":"Cancer Gene Ther"},{"key":"1829_CR22","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nri3665","volume":"14","author":"A Iwasaki","year":"2014","unstructured":"Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol. 2014;14:315\u201328.","journal-title":"Nat Rev Immunol"},{"key":"1829_CR23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41590-021-01091-0","volume":"23","author":"MS Diamond","year":"2022","unstructured":"Diamond MS, Kanneganti TD. Innate immunity: the first line of defense against SARS-CoV-2. Nat Immunol. 2022;23:165\u201376.","journal-title":"Nat Immunol"},{"key":"1829_CR24","doi-asserted-by":"publisher","first-page":"287","DOI":"10.4161\/auto.22831","volume":"9","author":"M Ambj\u00f8rn","year":"2013","unstructured":"Ambj\u00f8rn M, Ejlerskov P, Liu Y, Lees M, J\u00e4\u00e4ttel\u00e4 M, Issazadeh-Navikas S. IFNB1\/interferon-\u03b2-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function. Autophagy. 2013;9:287\u2013302.","journal-title":"Autophagy"},{"key":"1829_CR25","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41392-022-00921-3","volume":"7","author":"D Song","year":"2022","unstructured":"Song D, Jia X, Liu X, Hu L, Lin K, Xiao T, et al. Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors. Signal Transduct Target Ther. 2022;7:100.","journal-title":"Signal Transduct Target Ther"},{"key":"1829_CR26","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/gt.2009.161","volume":"17","author":"F Galivo","year":"2010","unstructured":"Galivo F, Diaz RM, Wongthida P, Thompson J, Kottke T, Barber G, et al. Single-cycle viral gene expression, rather than progressive replication and oncolysis, is required for VSV therapy of B16 melanoma. Gene Ther. 2010;17:158\u201370.","journal-title":"Gene Ther"},{"key":"1829_CR27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1158\/1078-0432.CCR-16-0477","volume":"23","author":"X Li","year":"2017","unstructured":"Li X, Wang P, Li H, Du X, Liu M, Huang Q, et al. The efficacy of oncolytic adenovirus is mediated by T-cell responses against virus and tumor in Syrian hamster model. Clin Cancer Res. 2017;23:239\u201349.","journal-title":"Clin Cancer Res"},{"key":"1829_CR28","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1001\/jamaoncol.2025.2374","volume":"11","author":"N Saleem","year":"2025","unstructured":"Saleem N, Wang J, Rejuso A, Teixeira-Pinto A, Stephens JH, Wilson A, et al. Outcomes of solid organ transplant recipients with advanced cancers receiving immune checkpoint inhibitors: a systematic review and individual participant data meta-analysis. JAMA Oncol. 2025;11:1150\u20139.","journal-title":"JAMA Oncol"},{"key":"1829_CR29","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1111\/tri.14115","volume":"34","author":"U Maggiore","year":"2021","unstructured":"Maggiore U, Palmisano A, Buti S, Claire Giudice G, Cattaneo D, Giuliani N, et al. Chemotherapy, targeted therapy and immunotherapy: which drugs can be safely used in the solid organ transplant recipients? Transpl Int. 2021;34:2442\u201358.","journal-title":"Transpl Int"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01829-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01829-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01829-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:04:31Z","timestamp":1787040271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01829-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1829"],"URL":"https:\/\/doi.org\/10.1038\/s41401-026-01829-2","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"19 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Wen-bo Zhu and Guang-mei Yan hold equity in Guangzhou Virotech Pharmaceutical Technology Co., Ltd. The remaining authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}