{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:51:40Z","timestamp":1792083100484,"version":"4.4.0"},"reference-count":47,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"abstract":"<jats:p>Introduction: The effects of adjuvant hyperthermia on glioblastoma-associated astrocytes remain poorly characterized. This study aimed to investigate the role of the purinergic P2X7 receptor, an ATP-gated ion channel, in mediating heat-induced astrocyte activation and its impact on tumor progression. Methods: Primary mouse astrocytes were subjected to heat stress (mild hyperthermia at 42\u00b0C). P2X7 signaling was examined using a specific antagonist (A-740003), siRNA-mediated knockdown, and live-cell calcium imaging. Astrocyte activation was evaluated by assessing glial fibrillary acidic protein expression and pro-inflammatory markers. The pro-tumorigenic potential of astrocyte-conditioned medium was tested on U87 glioblastoma cells. An orthotopic mouse model was used to validate the effects of local hyperthermia, with or without P2X7 inhibition. Results: Mild hyperthermia upregulated P2X7 expression in astrocytes and induced a substantial calcium influx, leading to activation of the calcineurin-NFAT pathway. This process promoted a reactive astrocyte phenotype and a pro-tumorigenic secretory profile, enhancing U87 cell proliferation, migration, and invasion. In vivo, mild hyperthermia was associated with increased tumor progression, which was attenuated by pharmacological inhibition of P2X7. Conclusion: Heat stress facilitates glioblastoma progression by activating astrocytes through the P2X7-mediated calcium-calcineurin-NFAT signaling pathway. These findings highlight P2X7 as a potential therapeutic target for optimizing hyperthermia-based strategies in glioblastoma treatment.<\/jats:p>","DOI":"10.1159\/000552781","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T16:01:26Z","timestamp":1786032086000},"page":"372-389","source":"Crossref","is-referenced-by-count":0,"title":["Heat Stress-Activated P2X7 Receptor Induces Astrocyte Activation and Regulates Glioma Tumor Microenvironment via Calcium Signaling 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