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Previously, we showed the antitumoral efficacy of nanoliposomal form of Epacadostat (Lip-EPA), as an IDO1 inhibitor. Herein, we used Lip-EPA as a combination approach with liposomal gp100 (Lip-gp100) anti-cancer vaccine in melanoma model. Here, we showed that B16F10 tumor express IDO1 so using Lip-EPA will enhance the efficacy of vaccine therapy. The biodistribution of ICG-labelled liposomal form of EPA showed the remarkable accumulation of drug at tumor site. In an in vivo study, Lip-EPA enhanced the antitumor efficacy of Lip-gp100 in which the IDO mRNA expression was decreased (~\u2009fourfold) in tumor samples. Also, we identified a significant increase in the number of infiltrated T lymphocytes (p\u2009&lt;\u20090.0001) with enhanced in interferon gamma (IFN-\u03b3) production (p\u2009&lt;\u20090.0001). Additionally, Lip-EPA\u2009+\u2009Lip-gp100 significantly modulated intratumoral regulatory T cells which altogether resulted in the highest delay in tumor growth (TGD\u2009=\u200956.54%) and increased life span (ILS\u2009&gt;\u200947.36%) in treated mice. Our study demonstrated that novel combination of Lip-EPA and Lip-gp100 was effective treatment with capability of being used in further clinical studies.\n<\/jats:p>","DOI":"10.1038\/s41598-023-31007-x","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T10:02:42Z","timestamp":1681120962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting the tumor microenvironment by liposomal Epacadostat in combination with liposomal gp100 vaccine"],"prefix":"10.1038","volume":"13","author":[{"given":"Sahar","family":"Tahaghoghi-Hajghorbani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Yazdani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin Reza","family":"Nikpoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Hatamipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abolghasem","family":"Ajami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Reza","family":"Jaafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Badiee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Rafiei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"issue":"2","key":"31007_CR1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ddmec.2005.05.017","volume":"2","author":"AJ Wagner","year":"2005","unstructured":"Wagner, A. 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