{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:06:44Z","timestamp":1790831204413,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG HA 8481\/1-1"],"award-info":[{"award-number":["DFG HA 8481\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB\/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR\/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions responding with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo.<\/jats:p>","DOI":"10.3390\/cancers13123058","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T22:00:02Z","timestamp":1624226402000},"page":"3058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Nectin-1 Expression Correlates with the Susceptibility of Malignant Melanoma to Oncolytic Herpes Simplex Virus In Vitro and In Vivo"],"prefix":"10.3390","volume":"13","author":[{"given":"Barbara","family":"Schwertner","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Lindner","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Toledo","family":"Toledo Stauner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Klapproth","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Magnus","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Rohrhofer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-5425","authenticated-orcid":false,"given":"Beatrice","family":"Schuler-Thurner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"\u00d6ttl","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Feichtgruber","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Drexler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Evert","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Krahn","sequence":"additional","affiliation":[{"name":"Medical Cell Biology, Internal Medicine D, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Berneburg","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0059-0349","authenticated-orcid":false,"given":"Barbara","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"},{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schuster","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/sj.gt.3301885","article-title":"ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties","volume":"10","author":"Liu","year":"2003","journal-title":"Gene Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7005","DOI":"10.1128\/JVI.72.9.7005-7011.1998","article-title":"The second-site mutation in the herpes simplex virus recombinants lacking the gamma134.5 genes precludes shutoff of protein synthesis by blocking the phosphorylation of 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