# Composition of Immune Cells in Sporadic Vestibular Schwannomas with Different Tumor Volumes

## TL;DR

This study explores how immune cells in vestibular schwannomas vary with tumor size, suggesting potential for new therapies.

## Contribution

The study is the first to comprehensively characterize immune-cell infiltration in sporadic vestibular schwannomas.

## Key findings

- Larger tumors had more T-helper and cytotoxic T cells, as well as specific macrophage and PD-1/PD-L1 positive cells.
- Increased CD274+ tumor cells were found in larger vestibular schwannomas.
- Immune cell diversity correlates with tumor size, indicating a role in disease progression.

## Abstract

The size of sporadic vestibular schwannomas is known to be associated with a high number of macrophages. In many other tumors, macrophages, as well as other immune cells like monocytes or T cells, influence tumor size and tumor progression. Therefore, the aim of this study was to characterize the presence of different immune cells based on their surface proteins in sporadic vestibular schwannomas and to investigate their possible influence on tumor size. A better understanding of the immune cells present in VS could lead to the development of drug therapies for VS, which are not available for sporadic VS at the moment.

Background/Objectives: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle. In preliminary studies, macrophage infiltration has been suggested to influence disease progression. However, the infiltration of other immune cells in VS remains largely unexplored. The aim of this study was to comprehensively characterize the immune cells in sporadic VS. Methods: Cryosections of five tumor samples from VS patients with different tumor volumes were examined. The abundance of fourteen immune-cell markers, one vascular marker, and two tumor markers were detected using multi-epitope ligand cartography (MELC). This enabled the spatial distribution and colocalization of immune- and tumor cell markers to be examined. Furthermore, using qPCR and bulk RNAseq, the mRNA levels of the immune-cell markers were examined in 204 VS samples of different tumor sizes. Results: VSs with greater tumor volumes showed an increased number of immune cells, more precisely T-helper cells (TH cells), cytotoxic T cells (Tc cells), CD68+, and CD163+ macrophages, as well as CD279+ (PD-1) and CTLA4+ cells (p < 0.05). In addition, an increased number of CD274+ (PD-L1) tumor cells were detected in VSs with higher tumor volume (p < 0.05). Conclusions: These results indicate that an increased diversity of immune-cell subtypes influences VS tumor size. Thus, novel diagnostic and therapeutic options could be developed by targeting the tumor-associated immune-cell populations in VSs.