{
  "abstract": "Pediatric posterior fossa group A (PFA) ependymoma is an aggressive, chemo-resistant brain tumor with a poor 10-year overall survival and no therapeutic options at relapse. Although conventionally classified as immune-cold, the spatial organization and therapeutic relevance of its rare immune infiltrates remain poorly characterized. Here, we present a spatially resolved immune analysis of 14 PFA ependymoma sections using published Visium spatial transcriptomics data analyzed through a multi-stage immune-focused computational framework combining reference-guided deconvolution, functional lymphocyte state scoring, ligand-receptor inference, and {beta}/{gamma}{delta} T cell immunotherapy opportunity scoring. Lymphocyte-associated hotspots were identified in 6 of 14 sections and, among confidently classified hotspots, were dominated by inflammatory-associated and retention-associated transcriptional states rather than cytotoxic or exhausted programs. These hotspots were preferentially confined to myeloid- and mesenchymal-rich tumor zones with near-complete exclusion from epithelial regions; ligand-receptor analysis identified four candidate restriction axes (SPP1-CD44, FN1-integrin, collagen VI-integrin, and APP-CD74). Immunotherapy opportunity scoring revealed heterogeneous and spatially compartmentalized {beta} and {gamma}{delta} T cell recognition landscapes across sections: {beta}T ligand availability and immunosuppressive tone both rose in the mesenchymal compartment, while the two components of {gamma}{delta} phosphoantigen-mediated recognition were spatially and transcriptionally dissociated from one another. Together, these findings reframe PFA ependymoma not as a monolithic immune desert but as a tumor type with spatially compartmentalized, mechanistically tractable immune niches, and provide a generalizable computational strategy for mapping immune architecture and T cell therapy susceptibility in low-infiltrated pediatric CNS tumors.",
  "abstract_shown": true,
  "affiliations": [
    "Karolinska Institutet"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "P. Truong"
    },
    {
      "name": "R. Mirzazadeh"
    },
    {
      "name": "J. Lundeberg"
    },
    {
      "name": "K. Blomgren"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Boutin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fr1ckk3rddb84.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754209",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1.full",
  "id": "fr1ckk3rddb84",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7214630780",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fr1ckk3rddb84.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:48Z",
      "native_id": "10.64898/2026.09.24.754209",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Spatial immune profiling reveals lymphocyte confinement to myeloid-mesenchymal niches and heterogeneous therapeutic T-cell opportunity in pediatric ependymoma",
  "title_text": "Spatial immune profiling reveals lymphocyte confinement to myeloid-mesenchymal niches and heterogeneous therapeutic T-cell opportunity in pediatric ependymoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:48Z",
  "url": "https://research.draconitic.com/paper/fr1ckk3rddb84",
  "venue": "bioRxiv",
  "versions": []
}