Single-cell multi-omic techniques highlight the diverse composition and intercellular interactions of the vestibular schwannoma tumor microenvironment.

Vestibular schwannomas (VS) are tumors arising from Schwann cells of the vestibulocochlear nerve, often leading to hearing loss, gait imbalance, and other neurological complications. Recently, molecular profiling of VS using bulk and single-cell transcriptional and epigenetic approaches has reshaped our understanding of VS pathogenesis and challenged the long-standing view of VS being molecularly homogeneous. These integrative, multi-omic approaches reveal significant differences within VS and highlight diverse Schwann cell subpopulations and their interactions with the tumor microenvironment. Interestingly, these analyses also uncover 2 molecularly distinct groups of VS, one containing Schwann cells with an "Injury-like" phenotype that drives VS progression through immune cell recruitment and another containing more quiescent Schwann cells with decreased immune cell infiltrate. In this review, we combine insights from modern molecular analyses of VS to provide an updated view of VS pathogenesis and mechanisms of tumor growth, which may be used to inform the development of novel treatments for VS.