Abstract
INTRODUCTION: Glioblastoma (GBM) represents the deadliest primary intracranial neoplasm. While many studies have focused on T cell responses to GBM, few have examined the role of humoral immunity. Here, we sought mechanistic insights into the anatomy and function of the humoral response against GBM. METHODS: C57BL/6J mice were injected stereotactically with syngeneic SB28 tumor cells. Humoral immunity was evaluated in the spleen and blood by high parameter flow cytometry and the meninges, brain, and spleen by confocal microscopy. The function importance of humoral immunity was interrogated using CD4-/- and IgA-/- mice and via transcranial application of the plasma cell survival factor, APRIL. RESULTS: High parameter flow cytometry revealed a significant increase of plasma B cells (CD19+, CD138+) in the spleen and blood of GBM mice within two weeks. Using blimp-1 reporter mice, we observed that IgA+ plasma cells localized to extrafollicular splenic regions and along meningeal dural venous sinuses near newly generated blood and lymphatic vessels that connected directly to the tumor. Decreased survival was observed in IgA-/- but not CD4-/- mice injected with SB28 cells, suggesting that a T helper independent IgA response plays a role in controlling GBM. This response was enhanced therapeutically by transcranial application of APRIL. CONCLUSION: Our results demonstrate that GBM elicits a systemic and meningeal humoral response, which plays in limiting GBM growth and can be transcranially enhanced via APRIL. The participation of IgA+ plasma cells in GBM immunity offers new possibilities for therapeutic intervention in this deadly disease.