Presenter: Mr Mike Haley, University of Manchester.
Title of talk: Deconstructing and targeting the tumour microenvironment in neurofibromatosis type 2 (NF2)
Abstract: NF2-related schwannomatosis (NF2 SWN) is a rare disease characterised by the growth of multiple nervous system neoplasms, including bilateral vestibular schwannoma (VS). VS tumours are characterised by extensive leukocyte infiltration. However, the immunological landscape in VS and the spatial determinants within the tumour microenvironment that shape the trajectory of disease are presently unknown. In the Brough and Couper labs, we have begun to deconstruct the immunological networks across VS, with hopes of identifying new targets for treatment. Using imaging mass cytometry (IMC) and single-cell RNA sequencing, we have spatially mapped the neoplastic cell, myeloid cell and T cell populations within established histological regions in NF2 SWN (Antoni A vs Antoni B). This showed that T-cells have spatially-defined interactions with tumour-associated macrophages (TAMs) in Antoni A regions, limiting to their ability to interact with tumorigenic Schwann cells. This spatial landscape is altered in Antoni B regions, where T-cell populations appear to interact with PD-L1+ Schwann cells. We also demonstrate that prior bevacizumab treatment (VEGF-A antagonist) preferentially reduces alternatively activated-like TAMs, whilst enhancing CD44 expression, in bevacizumab-treated tumours. Together, we describe niche-dependent modes of T-cell regulation in NF2 SWN VS, indicating the potential for microenvironment-altering therapies for VS
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