Immune Microenvironment of Vestibular Schwannomas

Background Vestibular schwannomas exhibit a variable natural history of growth, stability, or even spontaneous regression. Regulation by the immune system serves as an important biological influence on the growth pattern of tumors. We hypothesized that schwannomas exhibit a variable immune profile which may influence their behavior, and sought to characterize this immune microenvironment.

Method Ninety vestibular schwannomas and 3 normal brain tissue were evaluated for expression of the immune regulators PD-L1, TIM3, OX40, and LAG3; the T cell and macrophage markers CD4, CD8, CD45, CD68, and CD163.

Results Negative regulators of the immune system, including PD-L1 and TIM-3, were elevated in vestibular schwannomas compared with normal brain. In contrast, OX40, a marker of T cell activation, was lower in vestibular schwannomas, on average, compared with normal brain. Notably, although CD8-expressing T cells were higher among vestibular schwannomas compared with controls, LAG3, a marker of T cell exhaustion was also markedly elevated. Furthermore, extensive macrophage infiltration was observed as detected by CD68 and CD163, which was significantly elevated compared with that in normal brain tissues and partially concentrated around perivascular regions. On an individual tumor basis, significant variability was also present across schwannoma samples for all markers.

Conclusion Vestibular schwannomas demonstrate variable expression of immune regulatory markers as well as immune infiltrates. Elevated expression of several negative regulators of the immune response as well as evidence of T cell exhaustion suggests that tumor-associated inflammation orchestrated with local immunosuppression may play a critical role in these tumors. Future exploration for the role of immune modulation in select schwannomas may reveal relationships with their natural history and suggest potential therapeutic avenues for control of tumor growth.