{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:55:15Z","timestamp":1791190515943,"version":"4.1.0"},"reference-count":40,"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. Immunol."],"abstract":"<jats:p>Glioblastoma (GBM) combines heterogeneous vascular dysfunction with a predominantly myeloid immune landscape. This Mini Review focuses on a specific problem: vascular permeability is not equivalent to productive leukocyte access. Entry requires endothelial capture, chemokine-guided arrest, transendothelial migration, release from perivascular sites, intratumoral dispersion, target recognition, and sustained effector function. Human tissue and spatial studies show regionally distinct neurovascular and myeloid states, whereas much of the causal evidence for trafficking and retention remains preclinical. We therefore distinguish published observations from a hypothesis-generating model in which the blood-brain tumor barrier (BBTB) and perivascular myeloid niche can act as coupled but separable checkpoints. The main conceptual advance is not the already recognized heterogeneity of the BBTB, but the argument that leakage-based imaging should not be used as a surrogate for immune-cell entry and that each trafficking stage requires its own pharmacodynamic readout. We summarize regional BBTB states, differential lymphoid and myeloid access, and selected strategies\u2014vascular normalization, myeloid reprogramming, local cell delivery, and focused ultrasound\u2014while emphasizing their evidence limits. Clinical translation will require spatially registered human sampling, explicit model provenance, and tests that can reject individual components of the framework.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1957858","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:37:23Z","timestamp":1791189443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The blood-brain tumor barrier as a spatial immune checkpoint in glioblastoma: leukocyte entry, perivascular retention, and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Fangbo","family":"Lin","sequence":"first","affiliation":[{"name":"Rehabilitation Medicine Department, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and other primary brain malignancies in adults: a review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.1024","article-title":"Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: The CheckMate 143 phase 3 randomized clinical trial","volume":"6","author":"Reardon","year":"2020","journal-title":"JAMA Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0337-7","article-title":"Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma","volume":"25","author":"Cloughesy","year":"2019","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0339-5","article-title":"Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma","volume":"25","author":"Schalper","year":"2019","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02893-z","article-title":"Intrathecal bivalent CAR T cells targeting EGFR and IL13R\u03b12 in recurrent glioblastoma: phase 1 trial interim results","volume":"30","author":"Bagley","year":"2024","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2314390","article-title":"Intraventricular CARv3-TEAM-E T cells in recurrent glioblastoma","volume":"390","author":"Choi","year":"2024","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","article-title":"The blood-brain barrier and blood-tumour barrier in brain tumours and metastases","volume":"20","author":"Arvanitis","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox175","article-title":"Is the blood-brain barrier really disrupted in all glioblastomas? 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