Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca2+ activity
Menée à l'aide de modèles de gliomes d'origine humaine ou murine, cette étude met en évidence un mécanisme par lequel un accident vasculaire cérébral favorise la progression tumorale via le remodelage du microenvironnement tumoral, notamment via l'émergence d'une sous-population d'astrocytes associés à la tumeur se caractérisant par une réduction de l'activité calcique et par l'augmentation du nombre de macrophages TAM, deux processus liés respectivement aux régulateurs SLC4A4 et CCL2
Epidemiological studies suggest that persons with a history of stroke are at increased risk of developing brain tumors, yet the mechanisms linking brain injury to glioma progression remain unclear. Here we show that stroke promotes tumor infiltration into injured brain regions in human and mouse glioma models, accompanied by reduced overall survival. Stroke induces remodeling of the tumor microenvironment, including the emergence of a distinct population of tumor-associated astrocytes (TAAs) with diminished Ca2+ activity at the invasive front and enrichment of tumor-associated microglia and macrophages (TAMs). Restoring TAA Ca2+ signaling or TAM depletion suppresses stroke-induced glioma progression, identifying both populations as critical mediators of the injury response. Mechanistically, we identified SLC4A4 as a key regulator of Ca2+ activity in TAAs and CCL2-mediated TAM recruitment. Collectively, our findings establish stroke-induced remodeling of astrocytic Ca2+ signaling and TAMs as drivers of glioma progression and link brain injury to malignant disease.
Nature Cancer , article en libre accès, 2026