Proceedings of the National Academy of Sciences· 2026Q1
Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing
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- Q1SCImago
- 2026year
Short summary
Directly delivering interferon-gamma (IFNγ) into medulloblastoma tumors in mice significantly enhanced CD8+ T cell-mediated tumor cell killing and prolonged survival.
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Key points
- Medulloblastomas are immunologically cold tumors with impaired antigen presentation.
- T cell-derived IFNγ is essential for controlling medulloblastoma by inducing MHC class I on tumor cells.
- Depleting CD8+ T cells accelerated tumor growth in mice, while adoptive transfer prolonged survival.
- Local delivery of IFNγ into tumors enhanced CD8+ T cell killing and significantly prolonged survival in mice.
AI-generated from the title and abstract; the full text is not read.
Abstract
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.
The authors' abstract, as published at the source. Proceedings of the National Academy of Sciences, 2026 · DOI ↗
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Field: Genetics (Medicine)
GeneticsMedicine