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Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed immunological memory against these tumors. In addition, Delta-24-ACT was safe and caused no local or systemic toxicity. Mechanistic studies showed that Delta-24-ACT modulated the tumor-immune content, not only increasing the number, but also improving the functionality of immune cells. All of these data highlight the safety and potential therapeutic benefit of Delta-24-ACT the treatment of patients with DIPG.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.154812","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T08:36:17Z","timestamp":1649406977000},"source":"Crossref","is-referenced-by-count":22,"title":["Exploiting 4-1BB immune checkpoint to enhance the efficacy of oncolytic virotherapy for diffuse intrinsic pontine gliomas"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-7295","authenticated-orcid":true,"given":"Virginia","family":"Laspidea","sequence":"first","affiliation":[{"name":"Health Research Institute of Navarra, Pamplona, Navarra, Spain."},{"name":"Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Navarra, Spain."},{"name":"Department of Pediatrics, Navarra University Clinic, Pamplona, 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