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Our previous single-cell RNA sequencing analysis of oHSV-treated medulloblastoma tumors revealed expansion and activation of tumor-infiltrating dendritic cells (DCs), and direct oHSV infection of DCs within the brain. While the therapeutic effects of oHSVs have been primarily attributed to tumor cell infection, we hypothesize that direct infection of DCs also contributes to therapeutic efficacy by promoting DC maturation and immune activation. Although the oHSV infection in DCs was abortive, it led to increased expression of major histocompatibility complex (MHC) class I\/II and co-stimulatory molecules. oHSV-infected DCs activated na\u00efve CD4+ and CD8+ T cells, inducing expression of CD69 and CD25. These primed T cells exhibited enhanced cytotoxicity against CT-2A glioma cells. Adoptive transfer of oHSV-infected DCs via subcutaneous injection near inguinal lymph nodes delayed tumor growth in a syngeneic CT-2A glioma model, independent of tumor viral replication and lysis. Mechanistically, our in vitro studies demonstrate that oHSV can directly infect and functionally activate DCs, enabling them to prime effective anti-tumor T cell responses. This study highlights the anti-tumor potential of leveraging oHSV-infected DCs to augment viroimmunotherapy as a cancer therapeutic.<\/jats:p>","DOI":"10.3390\/v17081134","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:56:06Z","timestamp":1755590166000},"page":"1134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct oHSV Infection Induces DC Maturation and a Tumor Therapeutic Response"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5716-8664","authenticated-orcid":false,"given":"Doyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kelly","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0914-9480","authenticated-orcid":false,"given":"Jack","family":"Hedberg","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"College of Medicine, The Ohio State University, Columbus, OH 43220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-7910","authenticated-orcid":false,"given":"Alexia K.","family":"Martin","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"College of Medicine, The Ohio State University, Columbus, OH 43220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-523X","authenticated-orcid":false,"given":"Ilse","family":"Hernandez-Aguirre","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"College of Medicine, The Ohio State University, Columbus, OH 43220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0653-077X","authenticated-orcid":false,"given":"Yeaseul","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily R.","family":"Cain","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-2128","authenticated-orcid":false,"given":"Ravi","family":"Dhital","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-9051","authenticated-orcid":false,"given":"Kevin A.","family":"Cassady","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43220, USA"},{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Frosina, G. 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