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Oral dysplasia is the most common premalignancy in the oral cavity and yet it is insufficiently researched and thus both diagnosing and treating oral dysplasia are still problematic issues. This study focuses on the immune signature of oral dysplasia and explores whether stimulating the immune system with an immune therapy, vidutolimod (\u00b1\u2009immune checkpoint blockade (ICB)), can prevent the progression of oral dysplasia or even cause regression. Vidutolimod, a virus-like particle encapsulating G10, is believed to activate plasmacytoid dendritic cells (pDCs) through the activation of the Toll-like receptor 9 (TLR9). To investigate this, an established murine model for inducing oral cancer was used to study oral dysplasia development and response to in situ injection of vidutolimod at the premalignant phase. The effect of treatment was analyzed histologically and immunologically. ELISA revealed significantly elevated levels of IFN-\u03b3, IL-12, and TNF-\u03b1 in the sera of mice after 24\u00a0h of one treatment with vidutolimod\u2009+\u2009ICB as well as increased levels of proliferating T cells and pDCs in draining lymph nodes 72\u00a0h after the third and final treatment, thus indicating the immune-boosting effect of this therapy. Vidutolimod\u2009+\u2009ICB caused a significant decrease in Ki-67 expression by epithelial cells in the lesion area compared to untreated mice, implicating that this treatment regime may prevent lesion progression.<\/jats:p>","DOI":"10.1007\/s00262-025-04023-1","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T13:55:50Z","timestamp":1746280550000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In situ treatment with a TLR9 agonist virus-like particle to promote immune responses against oral epithelial dysplasia progression"],"prefix":"10.1007","volume":"74","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Mcmillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikesh","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin D.","family":"Lemke-Miltner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aseel O.","family":"Rataan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudartip","family":"Areecheewakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya S.","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Lanzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Geary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrean L.","family":"Simons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliasger K.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"issue":"4","key":"4023_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/sj.ebd.6401128","volume":"16","author":"A Anderson","year":"2015","unstructured":"Anderson A, Ishak N (2015) Marked variation in malignant transformation rates of oral leukoplakia. 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