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

TL;DR

This study shows that PD-L1 positivity in MenG C meningiomas indicates a more aggressive tumor type, which could help guide better treatment strategies.

Contribution

The paper identifies PD-L1 positivity as a marker for a hyperaggressive subgroup within MenG C meningiomas, independent of CDKN2A/B loss.

Findings

PD-L1 positivity is common in MenG C tumors but does not predict recurrence in MenG A and B tumors.

PD-L1 positivity occurs independently of CDKN2A/B loss in MenG C tumors.

Molecular profiling should be used to select patients for PD-1/PD-L1 immunotherapy trials.

Abstract

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.

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