{
  "abstract": "Meningioma is the most common primary intracranial tumor, yet recurrent and high-grade disease has few durable systemic options, and, unlike hematological malignancies, no systematically filtered cell-surface antigen resource exists to guide chimeric antigen receptor (CAR) T development. We address this gap not by nominating a trial-ready target but by building two reusable resources: an integrative meningioma surfaceome atlas and a transferable, gate-based framework that separates transcriptomic discovery from CAR-T target nomination. Analyzing single-cell RNA sequencing from eight meningioma patients (GSE183655; 80,220 quality-controlled cells), patient-aware differential expression followed by a curated surfaceome filter (UniProt plasma-membrane localization; extracellular domain ≥20 aa; exclusion of ribosomal, nuclear, cytoplasmic, and secreted proteins) reduced 83 scored candidates to 13 bona fide plasma-membrane (Tier A) antigens, removing prominent false positives such as the nuclear proteins FOXC1 and MGMT, the cytoplasmic enzyme lactate dehydrogenase A (LDHA), and the secreted protein PTGDS. Because expression ranking establishes discovery but not CAR-T suitability, we then applied explicit nomination gates: a systemic-safety score integrating whole-body GTEx transcriptomics with Human Protein Atlas protein-level evidence; a membrane-topology tractability gate distinguishing antibody-accessible single-pass and GPI-anchored ectodomains from multi-pass transporters and tail-anchored proteins; and a safety × coverage metric. Under stringent thresholds (combined safety ≥0.55, tumor-cell detection fraction ≥50%, safety × coverage ≥0.30), no Tier A antigen qualified. Ubiquitously expressed antigens were correctly demoted, including the tetraspanin CD9 (53.2% tumor-cell coverage but pan-tissue protein expression and high plasma abundance), and the highest-ranked transporter SLC7A2 was demoted by multi-pass topology (largest extracellular loop 38 aa) despite favorable transcriptomic safety. Leukemia inhibitory factor receptor (LIFR), a single-pass type I receptor with a contiguous 789-aa ectodomain, was the only antibody-tractable nominee for experimental follow-up yet remained liability laden (combined safety 0.41; safety × coverage 0.135) and is not a validated target. Cross-dataset expression overlap (93.3%) reflected mRNA reproducibility, not CAR-T validity or clinical validation, and generic-antibody docking was exploratory only. All findings are transcriptomic and require surface-level confirmation. This work contributes a reproducible meningioma surfaceome atlas and a transferable nomination framework and shows that rigorous gating leaves no single antigen with a favorable safety × coverage × tractability profile, motivating bispecific and logic-gated CAR-T strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, Stanford University, Stanford, CA, United States.",
    "Geisel School of Medicine, Dartmouth College, Hanover, NH, United States.",
    "Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vivek Sanker"
    },
    {
      "affs": [
        1
      ],
      "name": "Dhanya Mahesh"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda Liverani"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew Alexander Abikenari"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhikai Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Debebe Theodros"
    },
    {
      "affs": [
        0
      ],
      "name": "Ravi Medikonda"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Jose Cavagnaro"
    },
    {
      "affs": [
        0
      ],
      "name": "Matei Alexandru Banu"
    },
    {
      "affs": [
        0
      ],
      "name": "Atman Desai"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael Lim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/198m40zwn7855.bib",
  "cited_by": 0,
  "doi": "10.3389/fbinf.2026.1919802",
  "fulltext_url": "https://europepmc.org/articles/PMC13677907",
  "id": "198m40zwn7855",
  "issns": [
    "2673-7647"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898508",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7220382401",
  "pdf_url": "https://europepmc.org/articles/PMC13677907?pdf=render",
  "pmcid": "PMC13677907",
  "pmid": "42898508",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/198m40zwn7855.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898508",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898508"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "An integrative meningioma surfaceome atlas and a transferable framework for CAR-T target nomination.",
  "title_text": "An integrative meningioma surfaceome atlas and a transferable framework for CAR-T target nomination.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/198m40zwn7855",
  "venue": "Frontiers in bioinformatics",
  "versions": []
}