Beyond Antoni: A Surgeon's Guide to the Vestibular Schwannoma Microenvironment

Abstract

Introduction Vestibular schwannomas (VS) are histologically benign tumors arising from cranial nerve VIII. Far from a homogenous proliferation of Schwann cells, mounting evidence has highlighted the complex nature of the inflammatory microenvironment in these tumors. Methods A review of the literature pertaining to inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in VS was performed. Relevant studies published up to June 2020 were identified based on a literature search in the PubMed and MEDLINE databases and the findings were synthesized into a concise narrative review of the topic. Results The VS microenvironment is characterized by a dense infiltrate of inflammatory cells, particularly macrophages. Significantly higher levels of immune cell infiltration are observed in growing versus static tumors, and there is a demonstrable interplay between inflammation and angiogenesis in growing VS. While further mechanistic studies are required to ascertain the exact role of inflammation in angiogenesis, tumor growth, and Schwann cell control, we are beginning to understand the key molecular pathways driving this inflammatory microenvironment, and how these processes can be monitored and targeted in vivo. Conclusion Observational research has revealed a complex and heterogeneous tumor microenvironment in VS. The functional landscape and roles of macrophages and other immune cells in the VS inflammatory infiltrate are, however, yet to be established. The antiangiogenic drug bevacizumab has shown the efficacy of targeted molecular therapies in VS and there is hope that agents targeting another major component of the VS microenvironment, inflammation, will also find a place in their future management.

Analysis of tumor microenvironment composition in vestibular schwannomas: insights into NF2-associated and sporadic variations and their clinical correlations

“…Emerging evidence underscores the increasing importance of immune cells within the microenvironment. Contrary to the conventional notion that only mutated Schwann cells bear relevance in VS pathogenesis, our findings reveal a substantial presence of immune cells, particularly macrophages, in these benign tumors ( 22 ).…”

The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma

“… 12 Inflammation is present in both sporadic and NF2 -SWN VS with similar levels of tumour-associated leukocyte infiltration, 8 , 13 , 14 and inflammation—specifically increased circulating chemokines and macrophage infiltration—correlates with increased sporadic VS growth. 15–18 Along with macrophage niches, tumour-infiltrating lymphocytes such as T-cells and, to a much lesser extent, B cells are found within both sporadic and NF2 -SWN VS. 19 , 20 Both macrophages and T-cells within the tumour immune microenvironment have garnered attention for their potentials as therapeutic targets in VS, 10 , 21 , 22 but as yet, no studies have aimed to identify whether targeted immunotherapeutics would be equally efficacious in both sporadic and NF2 -SWN VS, nor whether the more common sporadic VS samples could be used to assess therapeutics to treat NF2 -SWN VS and vice versa.…”

The significance of programed cell death‐ligand 1 expression in vestibular schwannoma

“…It has been recognized that immune cells, such as macrophages and B and T lymphocytes, infiltrate the VS (Hannan et al., 2020 ). Evidence from both ex vivo and in vivo studies showed that inflammation and the immune microenvironment in VS play a key role in the pathophysiology of VS, and research on targeted molecular therapies for VS has drawn attention (Hannan et al., 2022 ; Lewis et al., 2019 ). Although VS is a benign tumor, it appears that the immune system checkpoint can be circumvented by expressing PD‐L1.…”