Interferon Restores Antigen Presentation and Sensitizes Medulloblastoma to T Cell Killing

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ABSTRACT Medulloblastomas are commonly considered immunologically cold and refractory to immunotherapy. One contributing factor to their low immunogenicity is impaired antigen presentation, which allows tumor cells to escape from cytotoxic T cells. Here we use a syngeneic mouse model of medulloblastoma to study the role of CD8 + T cells in medulloblastoma growth. 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 anti-tumor effects rely on T cells secreting interferon gamma (IFNγ), which induces MHC class I on tumor cells and facilitates tumor cell killing by T cells. Notably, this response is essential for CD8 + T cell–mediated tumor attack, as blocking IFNγ signaling in vivo abrogates MHC class I induction and eliminates the beneficial effect of T cells. Importantly, delivering IFNγ directly into tumors via convection-enhanced delivery (CED) 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 tumor growth and the value of IFNγ as an adjuvant for T cell-based immunotherapy.

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