Local Anti–PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model

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dc.citation.firstpage767en_US
dc.citation.issueNumber8en_US
dc.citation.journalTitleCancer Prevention Researchen_US
dc.citation.lastpage778en_US
dc.citation.volumeNumber14en_US
dc.contributor.authorShi, Yewenen_US
dc.contributor.authorXie, Tong-xinen_US
dc.contributor.authorLeach, David G.en_US
dc.contributor.authorWang, Bingbingen_US
dc.contributor.authorYoung, Simonen_US
dc.contributor.authorOsman, Abdullah A.en_US
dc.contributor.authorSikora, Andrew G.en_US
dc.contributor.authorRen, Xiaoyongen_US
dc.contributor.authorHartgerink, Jeffrey D.en_US
dc.contributor.authorMyers, Jeffrey N.en_US
dc.contributor.authorRangel, Robertoen_US
dc.date.accessioned2021-08-20T20:24:27Zen_US
dc.date.available2021-08-20T20:24:27Zen_US
dc.date.issued2021en_US
dc.description.abstractAlthough the principle of systemic treatment to prevent the progression of oral premalignant lesions (OPL) has been demonstrated, there remains a lack of consensus about an optimal approach that balances clinical efficacy with toxicity concerns. Recent advances in cancer therapy using approaches targeting the tumor immune microenvironment (TIME) including immune-checkpoint inhibitors indicate that these agents have significant clinically activity against different types of cancers, including oral cancer, and therefore they may provide an effective oral cancer prevention strategy for patients with OPLs. Our past work showed that systemic delivery of a monoclonal antibody to the programmed death receptor 1 (PD-1) immune checkpoint can inhibit the progression of OPLs to oral cancer in a syngeneic murine oral carcinogenesis model. Here we report a novel approach of local delivery of a PD-1 immune-checkpoint inhibitor loaded using a hydrogel, which significantly reduces the progression of OPLs to carcinomas. In addition, we detected a significant infiltration of regulatory T cells associated with oral lesions with p53 mutation, and a severe loss of expression of STING, which correlated with a decreased infiltration of dendritic cells in the oral lesions. However, a single local dose of PD-1 inhibitor was found to restore stimulator of interferon response cGAMP interactor 1 (STING) and CD11c expression and increase the infiltration of CD8+ T cells into the TIME irrespective of the p53 mutational status. Overall, we provide evidence for the potential clinical value of local delivery of biomaterials loaded with anti–PD-1 antibodies to prevent malignant progression of OPLs. Prevention Relevance: Oral cancer is an aggressive disease, with an overall survival rate of 50%. Preinvasive histologic abnormalities such as tongue dysplasia represent an early stage of oral cancer; however, there are no treatments to prevent oral carcinoma progression. Here, we combined biomaterials loaded with an immunotherapeutic agent preventing oral cancer progression.en_US
dc.identifier.citationShi, Yewen, Xie, Tong-xin, Leach, David G., et al.. "Local Anti–PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model." <i>Cancer Prevention Research,</i> 14, no. 8 (2021) American Association for Cancer Research: 767-778. https://doi.org/10.1158/1940-6207.CAPR-20-0607.en_US
dc.identifier.digital767-fullen_US
dc.identifier.doihttps://doi.org/10.1158/1940-6207.CAPR-20-0607en_US
dc.identifier.urihttps://hdl.handle.net/1911/111310en_US
dc.language.isoengen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs International 4.0 License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleLocal Anti–PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Modelen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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