Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing
Menée à l'aide d'un modèle murin de médulloblastome, cette étude démontre que la délivrance intratumorale d'interféron gamma par convection restaure l'expression du complexe majeur d'histocompatibilité de classe I sur les cellules cancéreuses, sensibilise ces dernières à l'action des lymphocytes T CD8+ et prolonge de manière significative la survie
Medulloblastoma is the most common malignant brain tumor in children, associated with substantial long-term treatment toxicity and relapse. Immunotherapies remain largely ineffective in pediatric brain tumors, highlighting the need to overcome barriers to immune control. We demonstrate that impaired antigen presentation limits CD8+ T cell–mediated control of medulloblastoma and identify interferon gamma (IFNγ) as a key regulator that restores tumor antigen presentation. Convection-enhanced delivery of IFNγ into tumors upregulates MHC class I, increases CD8+ T cell–mediated killing, and significantly prolongs survival in mice. Our study repurposes IFNγ as a targeted immune modulator rather than a cytotoxic agent. Combined with locoregional delivery, this approach overcomes systemic side effects and may unlock the therapeutic potential of immunotherapy in these otherwise refractory tumors. Medulloblastomas are considered immunologically cold and refractory to immunotherapy. One factor contributing to their low immunogenicity is impaired antigen presentation, which allows tumor cells to evade cytotoxic T cells. Using a syngeneic mouse model of medulloblastoma, we demonstrate that despite low expression of MHC class I on tumor cells, depletion of CD8+ T cells accelerates tumor growth, whereas adoptive transfer of tumor-reactive CD8+ T cells prolongs survival. These antitumor effects rely on T cell–derived interferon gamma (IFNγ), which induces MHC class I on tumor cells and facilitates tumor cell killing by T cells. Importantly, delivering IFNγ directly into tumors via convection-enhanced delivery enhances CD8+ T cell–mediated killing of tumor cells and significantly prolongs survival in tumor-bearing mice. These studies highlight the importance of T cells in controlling brain tumors and the value of IFNγ as an adjuvant for T cell–based immunotherapy.
Proceedings of the National Academy of Sciences , article en libre accès, 2026