Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer
Menée à l'aide de modèles murins ainsi que d'échantillons d'ascites et d'échantillons tumoraux prélevés sur des patientes atteintes d'un cancer séreux ovarien de haut grade, cette étude met en évidence l'intérêt d'un chélateur du fer, la défériprone, pour améliorer la réponse immunitaire innée contre les tumeurs métastatiques
Iron accumulation in tumors contributes to disease progression and chemoresistance. While targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells towards an immunostimulatory state characterized by production of type I interferon (IFN) and overexpression of molecules that activate natural killer (NK) cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T cell-centric modalities.