Single cell RNA-Seq of meninges immune landscape in GBM

Using single cell sequencing and T-cell receptor tracking to analyze a unique cohort of GBM clinical samples and mouse-preclinical models in combination with genetic perturbations, photoactivable mice, in vivo mRNA delivery and engineered human CAR T cells, we identified MHC class II-dependent immune cell hubs in the dura that promote T-cell responses to GBM.

Dura-primed CD8+ T cells migrate to the tumor microenvironment (TME) and display enhanced effector functions against GBM. In mechanistic studies we established that this enhanced effector phenotype of dura-primed CD8+ T cells is driven by the expression of PLAC8, which stabilizes phosphorylated STAT5 via MDM2. Moreover, we identified dural IL-33 as inducer of PLAC8 expression in CD8+ T cells.