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.
