{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:54:29Z","timestamp":1791179669419,"version":"4.1.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>\n                    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 \u226520 aa; exclusion of ribosomal, nuclear, cytoplasmic, and secreted proteins) reduced 83 scored candidates to 13\n                    <jats:italic>bona fide<\/jats:italic>\n                    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 \u00d7 coverage metric. Under stringent thresholds (combined safety \u22650.55, tumor-cell detection fraction \u226550%, safety \u00d7 coverage \u22650.30), 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 \u00d7 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 \u00d7 coverage \u00d7 tractability profile, motivating bispecific and logic-gated CAR-T strategies.\n                  <\/jats:p>","DOI":"10.3389\/fbinf.2026.1919802","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:14Z","timestamp":1791178334000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An integrative meningioma surfaceome atlas and a transferable framework for CAR-T target nomination"],"prefix":"10.3389","volume":"6","author":[{"given":"Vivek","family":"Sanker","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanya","family":"Mahesh","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine, Dartmouth College","place":["Hanover, NH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Liverani","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew Alexander","family":"Abikenari","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Addenbrooke\u2019s Hospital","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debebe","family":"Theodros","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Medikonda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jose","family":"Cavagnaro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matei Alexandru","family":"Banu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atman","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0121314","DOI":"10.1371\/journal.pone.0121314","article-title":"A mass spectrometric-derived cell surface protein atlas","volume":"10","author":"Bausch-Fluck","year":"2015","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"E10988","DOI":"10.1073\/pnas.1808790115","article-title":"The in silico human surfaceome","volume":"115","author":"Bausch-Fluck","year":"2018","journal-title":"Proc. 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