{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:07:27Z","timestamp":1776870447584,"version":"3.51.2"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health - Ricerca corrente","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"Biolingus AG","award":["2018-2019"],"award-info":[{"award-number":["2018-2019"]}]},{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"publisher","award":["IG 21366 to G.S."],"award-info":[{"award-number":["IG 21366 to G.S."]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Salivary gland tumors are a heterogeneous group of neoplasms representing less than 10% of all head and neck tumors. Among salivary gland tumors, salivary duct carcinoma (SDC) is a rare, but highly aggressive malignant tumor resembling ductal breast carcinoma. Sublingual treatments are promising for SDC due to the induction of both local and systemic biological effects and to reduced systemic toxicity compared to other administration routes. In the present study, we first established that the sublingual administration of type I IFN (IFN-I) is safe and feasible, and exerts antitumor effects both as monotherapy and in combination with chemotherapy in transplantable tumor models, i.e., B16-OVA melanoma and EG.7-OVA lymphoma. Subsequently, we proved that sublingual IFN-I in combination with cyclophosphamide (CTX) induces a long-lasting reduction of tumor mass in NeuT transgenic mice that spontaneously develop SDC. Most importantly, tumor shrinkage in NeuT transgenic micewas accompanied by the emergence of tumor-specific cellular immune responses both in the blood and in the tumor tissue. Altogether, these results provide evidence that sublingual IFN holds promise in combination with chemotherapy for the treatment of cancer.<\/jats:p>","DOI":"10.3390\/cells10040845","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T10:34:39Z","timestamp":1617878079000},"page":"845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anticancer Effects of Sublingual Type I IFN in Combination with Chemotherapy in Implantable and Spontaneous Tumor Models"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria","family":"Ciccolella","sequence":"first","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3437-9288","authenticated-orcid":false,"given":"Donatella","family":"Negri","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Pacca","sequence":"additional","affiliation":[{"name":"Animal Research and Welfare Centre, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"D\u2019Urso","sequence":"additional","affiliation":[{"name":"Animal Research and Welfare Centre, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Macchia","sequence":"additional","affiliation":[{"name":"Animal Research and Welfare Centre, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9093-6803","authenticated-orcid":false,"given":"Rossella","family":"Canese","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Pang","sequence":"additional","affiliation":[{"name":"Biolingus AG, CH-6052 Hergiswil NW, Switzerland"},{"name":"Murdoch Children\u2019s Research Institute, Parkville 3052, Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Parkville 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"SaiYing Ko","sequence":"additional","affiliation":[{"name":"Biolingus AG, CH-6052 Hergiswil NW, 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