PD-L1 positivity predicts a unique hyperaggressive tumor group within MenG C meningiomas

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of CDKN2A/B loss, a core component of the WHO grade that is regularly used in clinical trial selection criteria. Our results indicate that future clinical trials for PD-1/PD-L1 centric immunotherapies should select patients after molecularly profiling tumors to confirm aggressive MenG C status.