{
  "abstract": "Background Glioblastoma (GBM) is the most aggressive form of cancer of the central nervous system. Despite advances in immunotherapies and standard-of-care treatments for GBMs, clinical outcomes remain limited—owing to the immunosuppressive tumor microenvironment and the intrinsic resistance of GBM to conventional approaches. As a result, there is growing interest in rational combination strategies, particularly those pairing oncolytic viruses with immune-based therapies or established treatment modalities. Oncolytic viruses, by displaying conditionally enabled tumor cell-restricted replication, while stimulating antitumor immune responses and leaving healthy tissue unharmed, have the potential to reshape the therapeutic landscape in GBM and aid in achieving more durable benefits for patients. This study investigates the use of infectious bursal disease virus (IBDV) as a potential virotherapy for GBM.Methods and results In vitro, IBDV infects and replicates within murine GBM cells and patient-derived GBM stem cells, inducing direct oncolysis and activating proinflammatory gene expression programs. IBDV also enhances the cytolytic activity of temozolomide (TMZ) in treated GBM cells, complementing TMZ chemotherapeutic activity. In vivo, treatment with IBDV in CT-2A GBM-bearing syngeneic mice significantly reduced tumor growth and improved survival compared with control mice. Intratumoral administration of IBDV induces a deep remodeling of the tumor immune microenvironment, reducing immunosuppressive M2-like macrophages and increasing the ratio of CD8+T cells to regulatory T cells. This reversion of immunosuppression linked to monocyte-derived macrophages has been confirmed on experimental ex vivo infections of explants derived from human GBM donors.Conclusion These findings support further consideration of IBDV as a novel virotherapeutic agent for GBM.",
  "authors": [
    {
      "affiliations": [
        "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA",
        "Microbiology Section, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain",
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain"
      ],
      "name": "Vicent Tur-Planells"
    },
    {
      "affiliations": [
        "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Yonina Bykov"
    },
    {
      "affiliations": [
        "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Gloria Dawodu"
    },
    {
      "affiliations": [
        "Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Community of Madrid, Spain"
      ],
      "name": "Noemi García-Romero"
    },
    {
      "affiliations": [
        "Microbiology Section, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain",
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain"
      ],
      "name": "Sara Izpura-Luis"
    },
    {
      "affiliations": [
        "Department of Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA"
      ],
      "name": "Leticia Pérez-Rodríguez"
    },
    {
      "affiliations": [
        "Microbiology Section, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain",
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain"
      ],
      "name": "Sergio Rius-Rocabert"
    },
    {
      "affiliations": [
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain"
      ],
      "name": "Irina Palacín-Aliana"
    },
    {
      "affiliations": [
        "Microbiology Section, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain",
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain",
        "National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain"
      ],
      "name": "Javier Arranz-Herrero"
    },
    {
      "affiliations": [
        "National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain"
      ],
      "name": "Inmaculada Márquez-Leiva"
    },
    {
      "affiliations": [
        "Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Community of Madrid, Spain"
      ],
      "name": "Alvaro Monago-Sanchez"
    },
    {
      "affiliations": [
        "Laboratorio de Inmunobiología de Trasplante e Inmunoterapia, Instituto de Biología Molecular (INBIOMIC), Universidad de León, León, Spain"
      ],
      "name": "Maria-Luisa del Rio"
    },
    {
      "affiliations": [
        "Laboratorio de Inmunobiología de Trasplante e Inmunoterapia, Instituto de Biología Molecular (INBIOMIC), Universidad de León, León, Spain"
      ],
      "name": "Jose-Ignacio Rodriguez-Barbosa"
    },
    {
      "affiliations": [
        "Department of Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain"
      ],
      "name": "Jordi Cano-Ochando"
    },
    {
      "affiliations": [
        "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA",
        "Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"
      ],
      "name": "Adolfo García-Sastre"
    },
    {
      "affiliations": [
        "Centro de Investigación en ciencias de la alimentación CSIC-UAM, CIAL, Madrid, Community of Madrid, Spain"
      ],
      "name": "Daniel Lozano-Ojalvo"
    },
    {
      "affiliations": [
        "Microbiology Section, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain",
        "Department of Basic Medical Sciences, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain"
      ],
      "name": "Estanislao Nistal-Villan"
    },
    {
      "affiliations": [
        "Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Community of Madrid, Spain",
        "Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain",
        "Brain Tumour Laboratory, Fundación Vithas, Grupo Hospitales Vithas, Madrid, Spain"
      ],
      "name": "Angel Ayuso-Sacido"
    },
    {
      "affiliations": [
        "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA",
        "Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
        "Marc and Jennifer Lipschultz Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, NY, USA"
      ],
      "name": "Sara Cuadrado-Castano"
    }
  ],
  "title": "Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma",
  "uid": "d7728735-9a2d-5c85-8c70-51704eb5bc7c"
}