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Cytomegalovirus (CMV) has been implicated in tumor progression and modulation in glioblastoma. To investigate this potential connection, CMV-associated changes in the glioblastoma immune landscape were characterized in vitro and in a murine glioblastoma model. Infection of mouse glioblastoma cells (GL261Luc2) with mCMV resulted in a short period of viral replication. MHC-I cell surface expression was reduced after mCMV infection by approximately 40% compared with non-infected tumor cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Viral regulators of antigen presentation (vRAP) were shown to be responsible for MHC-I downregulation using a recombinant mCMV (\u0394vRAP) lacking the known immune evasion genes. RNA sequencing of mCMV infected GL261Luc cells revealed 2711 differentially expressed genes (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005). Of particular interest was the downregulation of MHC-I-associated genes <jats:italic>H2-Q1-10<\/jats:italic> and <jats:italic>Tap1<\/jats:italic> fter CMV infection. In vivo, the mCMV immediate early gene (IE1) was detected in brains of mCMV\u2009+\u2009animals after tumor implantation and increased during tumor growth. mCMV\u2009+\u2009mice had significantly shorter survival than controls, depending on initial tumor size (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Tumor immune infiltrates in mCMV infection were characterized by B cell infiltrates and low levels of NK cell infiltration. Here, the landscape of immune cell infiltrates is shifted toward B cell infiltration and reduced numbers of NK cells. CMV leads to immune evasion mediated MHC-I downregulation in murine glioblastoma. Thus, CMV infection in glioblastoma may contribute to unchecked tumor growth in glioblastoma by increasing immune evasion.<\/jats:p>","DOI":"10.1038\/s41598-025-10107-w","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T18:41:49Z","timestamp":1752777709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cytomegalovirus-induced oncomodulation drives immune escape in glioblastoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Harald","family":"Krenzlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Corr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Ailani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Einheuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bukur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"R\u00f6\u00dfler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Hollnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Dauth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Griessl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gutknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noe","family":"Mercado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Alessandri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Ringel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean E.","family":"Lawler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels A.","family":"Lemmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naureen","family":"Keric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"10107_CR1","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1200\/JCO.2017.73.0119","volume":"35","author":"BM Alexander","year":"2017","unstructured":"Alexander, B. 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