{
  "abstract": "Chimeric antigen receptor (CAR)-T cell therapy has shown limited efficacy in glioblastoma (GB), largely because of the immunosuppressive tumor microenvironment (TME). We have previously demonstrated that the ligand-based mCD70-directed construct mCAR27 specifically eliminates CD70⁺ GB cells in vitro, and induces durable tumor remission with prolonged survival in a syngeneic model of orthotopic GB. Despite the therapeutic promise of CD70 as a GB CAR-T cell target, the impact of CD70-directed CAR-T cells on the brain tumor immune landscape after target interception remains unexplored. Here, we independently confirmed a tumorigenic role for CD70 in murine GB by performing bulk RNA sequencing and in vivo experiments. Next, we applied single-cell RNA sequencing (scRNAseq) to decipher the transcriptome of GB-infiltrating immune cells in immunocompetent mice bearing CD70⁺ GB after intratumoral mCAR27 therapy. CAR-T cell treatment expanded adoptively transferred cells and was associated with increased endogenous Cd8⁺ T-cell infiltration, alongside a reduction in immunosuppressive populations, including Tregs and anti-inflammatory M2-like macrophages, but also subsets of dendritic and natural-killer cells. CD70 expression was detected on multiple GB-infiltrating immune subsets, notably Tregs and M2-like macrophages. Transcriptionally, mCAR27-mediated GB remission led to a coordinated downregulation of type-I interferon-stimulated genes and immunosuppressive mediators such as Arg1, Tgfbi, Cd274, Pdcd1lg2 and Lag3, coupled with upregulation of genes involved in inflammatory resolution, findings consistent with attenuation of GB-derived inflammatory stress and immunosuppression. Collectively, we showcase that CD70-directed CAR-T cell therapy remodels the post-treatment immune landscape towards resolution of inflammation and reduced immunosuppression, supporting sustained immune surveillance.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.",
    "Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.",
    "Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.",
    "Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.",
    "Medicine, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.",
    "Department of Neurology and Neurooncology Program, Heidelberg University Hospital, Heidelberg, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alexandros Kourtesakis"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Dennis Alexander Agardy"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Clara Tejido Dierssen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ling Hai"
    },
    {
      "affs": [
        0
      ],
      "name": "Dirk Carsten Frieder Hoffmann"
    },
    {
      "affs": [
        0
      ],
      "name": "Normann Mussnig"
    },
    {
      "affs": [
        3
      ],
      "name": "Ralph Sinn"
    },
    {
      "affs": [
        3
      ],
      "name": "Manuel Fischer"
    },
    {
      "affs": [
        0
      ],
      "name": "Andy Schacht"
    },
    {
      "affs": [
        3
      ],
      "name": "Michael Breckwoldt"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Lukas Bunse"
    },
    {
      "affs": [
        4
      ],
      "name": "Tim Sauer"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Michael Platten"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Wolfgang Wick"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Tobias Kessler"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0e6dzycb7d98n.bib",
  "cited_by": 0,
  "doi": "10.1080/2162402x.2026.2745295",
  "fulltext_url": "https://europepmc.org/articles/PMC13682394",
  "id": "0e6dzycb7d98n",
  "issns": [
    "2162-4011",
    "2162-402X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894313",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2716|Glioma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7222952400",
  "pdf_url": "https://europepmc.org/articles/PMC13682394?pdf=render",
  "pmcid": "PMC13682394",
  "pmid": "42894313",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0e6dzycb7d98n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42894313",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894313"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Glioma Diagnosis and Treatment",
      "subfield": "human-genetics"
    }
  ],
  "title": "Glioblastoma immune landscape remodeling following treatment with CD70-targeted CAR-T cells.",
  "title_text": "Glioblastoma immune landscape remodeling following treatment with CD70-targeted CAR-T cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/0e6dzycb7d98n",
  "venue": "Oncoimmunology",
  "versions": []
}