{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:25:13Z","timestamp":1793409913472,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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), the most aggressive diffuse glioma in adults, remains one of the most lethal malignancies of the central nervous system owing to its profound heterogeneity, near-universal recurrence, and marked resistance to therapy. Increasing evidence indicates that these features cannot be fully explained by genetic alterations alone but instead reflect a high degree of cancer cell plasticity shaped by dynamic interactions with the tumor microenvironment. In this review, we discuss how the tumor immune niche is associated with, and in selected experimental settings may influence, GBM cell-state transitions. Single-cell and spatial studies support the view that GBM cells may shift among NPC-like, OPC-like, AC-like, mesenchymal-like, stem-like, and stress-adapted states under immune, hypoxic, and therapeutic pressures. Among these influences, tumor-associated macrophages, microglia, inflammatory cytokines, and hypoxic or perivascular niches have been implicated in the enrichment of aggressive phenotypes and the maintenance of immunosuppressive ecosystems. We further highlight how plasticity-driven state transitions contribute to immune escape by enhancing myeloid recruitment, limiting effective T-cell function, and reinforcing mesenchymal and injury-response programs. Therapy adds another layer of complexity by inducing adaptive reprogramming in surviving cells, thereby fostering recurrence-associated states with increased resistance to treatment. Finally, we propose that durable GBM control will likely require combinatorial strategies that target both tumor cell plasticity and the immune niche that sustains it. Understanding this reciprocal relationship may reveal new therapeutic vulnerabilities and improve the design of future immunomodulatory and anti-plasticity interventions.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1857659","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:34Z","timestamp":1782452794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune niche-associated and niche-regulated plasticity in glioblastoma: state transitions, immune escape, and therapeutic vulnerabilities"],"prefix":"10.3389","volume":"17","author":[{"given":"Haijun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Shenzhen Baoan People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Baoan 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