Macrophage infiltration is associated with faster growth and increased vascularity in a large cohort of sporadic vestibular schwannomas

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Abstract

Background
There is evidence that macrophage infiltration in the tumor microenvironment (TME) promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular TME and tumor associated macrophages (TAMs) may represent another druggable target.

Objectives
We sought to characterise the relationship between growth, TAM infiltration and circulating monocyte chemokines in a large cohort of VS patients.

Methods
Immunostaining for Iba1 (macrophages), CD31 (endothelium) and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS.

Results
The Iba1+ cell count was significantly higher in growing as compared to static VS (592 vs. 226/x20 HPF, p=<0.001). Similarly, the CD31+ % surface area was higher in growing VS (2.19% vs. 1.32%, p=0.01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2=0.263, p=<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS.

Conclusion
There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a co-linear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.

Bibliographical metadata

Original languageEnglish
JournalNeurosurgery
Publication statusAccepted/In press - 21 Sep 2022