Background Previously, Vestibular Schwannomas (VS) were thought to arise as a consequence of the clonal expansion of neoplastic Schwann cells, but more recently there has been increasing interest in the role immune cell infiltration may play in their growth. The focus of this thesis was to investigate the link between immune cell infiltration and tumour growth, as well as to interrogate the relationship between inflammation and angiogenesis in VS. Methods 101 growing and 19 static/shrinking sporadic VS were subjected to immunostaining for Iba1, CD31 and fibrinogen. Plasma samples from 50 patients with growing VS and 25 patients with static VS were analysed to assess the circulating concentrations of 47 cytokines, chemokines and growth factors. Finally, immunostaining for proteins associated with Angiopoietin/Tie2 angiogenesis pathway was performed on sporadic NF2-Schwannomatosis associated VS and this was further validated with quantification of angiopoeitin 1 and angiopoeitin 2 expression. Results Growing VS were characterised by significantly higher infiltration of Iba1+ macrophages and increased microvessel surface area when compared to static tumours. There was a strong positive correlation between macrophage infiltration and VS growth rate, and this effect persisted following correction for tumour size. Significantly increased concentrations of IL-1ï¡, IL-6, IL12p40 and IL-18 were observed in the plasma of patients with growing VS, alongside CCL22, CXCL9 and CCL4 when compared to plasma obtained from patients with static VS. Conclusions This thesis provides clear evidence of a relationship between macrophage infiltration and VS growth. This macrophage infiltration may be driven by tumoral secretion of chemokines into the bloodstream and targeting these processes may yield therapeutic benefits in patients with sporadic and NF2-Schwannomatosis associated VS.
The Tumour Microenvironment in Vestibular Schwannoma
Hannan, C. (Author). 1 Aug 2023
Student thesis: Phd