{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:34:53Z","timestamp":1787582093965,"version":"build-2736575974"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"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>Osteosarcoma exhibits limited responsiveness to immune checkpoint blockade, a feature commonly referred to as immune coldness. However, interpreting immune coldness as a fixed tumour trait may underestimate the spatially and temporally dynamic processes that govern immune resistance. Accumulating evidence instead supports an evolutionary ecosystem view, in which tumour-intrinsic defects in immune recognition, lymphocyte exclusion, myeloid predominance, and metastatic niche formation collectively contribute to clinically non-productive immunity, rather than representing discrete or mutually exclusive stages. Single-cell, spatial, clinical, and translational studies further highlight pronounced heterogeneity among primary, treatment-exposed, and metastatic lesions, with particularly distinct immune architectures observed in pulmonary sites. In this context, lung metastases are not merely endpoints of dissemination, but active immune-modulatory niches in which macrophages, granulocytic myeloid-derived suppressor cells, fibroblasts, and spatially restricted lymphocytes jointly shape therapeutic resistance. These observations motivate a shift away from modality-centred therapeutic escalation toward immune state\u2013guided stratification, sequential reprogramming of the tumour ecosystem, and barrier-specific treatment strategies. Separating clinical evidence from patient-derived, translational, and preclinical findings further provides a framework for prioritizing spatial biomarkers, designing adaptive clinical trials, and developing lung-metastasis\u2013focused immunotherapeutic approaches.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1919497","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:51:44Z","timestamp":1787579504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic immune state transitions and metastatic niche remodelling drive osteosarcoma evolution as a barrier-restricted immune-cold ecosystem"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiangyou","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People\u2019s Hospital)","place":["Ganzhou, 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