ID #733 Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing
Robert Wechsler=Reya, Tanja Eisemann, Meher Beigi Masihi, Theophilos Tzaridis, Veronika Pister, Isaac Youm, Kendall Chambers, Aditi Dutta, Alexander Wenzel, Koei Chin, Scott Pomeroy, Jill Mesirov, Ernest Fraenkel, Anindya Bagchi, Lukas ChavezAbstract
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 (IFNg), which induces MHC class I on tumor cells and facilitates tumor cell killing. Notably, this response is essential for CD8+ T cell–mediated tumor attack, as blocking IFNg signaling in vivo abrogates MHC class I induction and eliminates the beneficial effect of T cells. Importantly, delivering IFNg 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 IFNg as an adjuvant for T cell-based immunotherapy.