Introduction: Vestibular schwannomas exhibit a variable natural history, with one-third demonstrating growth on extended observation and two-thirds maintaining a stable size or exhibiting spontaneous regression. Elucidation of the biological basis for this difference in natural history may open potential therapeutic avenues for control of tumor growth. We hypothesized that schwannomas exhibit a variable immune profile which may influence their behavior, and sought to characterize this immune microenvironment.
Methods: 90 vestibular schwannomas and 3 normal brain tissue were evaluated for expression of the immune checkpoints PD-L1 and PD-L2 by immunohistochemistry, as well as for lymphocytes infiltration by the T cell markers CD3, CD4, CD8, and FOXP3, and the macrophage markers CD163, CD68, and CD45.
Results: Compared with normal brain tissue, PD-L1 expression is dramatically increased in a majority of vestibular schwannomas, in contrast to PD-L2. While CD8+ cells and a low fraction of FOXP3+ cells were detected, CD3+ and CD4+ T lymphocytes were sparsely observed. Furthermore, extensive macrophage infiltration was observed as detected by CD163 and CD68, 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.
Conclusions: Elevated PD-L1 expression and macrophage infiltration, coupled with reduced T lymphocytes suggests perturbation of immune surveillance in a fraction of vestibular schwannomas. Tumor-associated inflammation orchestrated with local immunosuppression may provide rationale for future immunotherapy targeting of select schwannomas.
Patient Care: Improved understanding of the immune profile of vestibular schwannomas may open new therapeutic avenues.
Learning Objectives: By the conclusion of this session, participants should be able to:
1. Describe the primary tumor infiltrating immune cells in vestibular schwannomas.