Meningioma microenvironment harbors a rich immune landscape with therapeutic implications (Bulk RNA-seq part)

Effective therapeutic targets are urgently needed for aggressive meningiomas. Given the pivotal role of immune microenvironment in tumor progression, we developed a comprehensive atlas of the meningioma microenvironment. Using single-cell and bulk techniques, we revealed a rich immune infiltrate in 2,610 meningiomas, among the highest observed across 34 human cancer types. Macrophages predominated in meningioma, contrasting with the lymphoid dominance of peripheral blood, with meninges exhibiting an intermediate immune profile. Cellular states and phenotypes of both immune and tumor cells shift during tumor progression toward an earlier-stage immune-suppressive and proliferative profile in aggressive meningiomas. Using ex vivo patient-derived tumor organoids, we demonstrated inducible responses to STING activation, marked by elevated cytokine release, which were synergistic when combined with PD-1 blockade. Together, these findings provide an extensive resource on the cellular heterogeneity of the meningioma microenvironment and provide a framework for rational therapeutic modeling and strategy development. Overall design: A total of 47 human meningiomas (fresh frozen tumor tissues) resected at Brigham and Women's Neurosurgery were sent for bulk RNA-seq at the Broad Institute of MIT and Harvard.