Spatial mapping of immune cell environments in NF2-related schwannomatosis vestibular schwannoma

Adam P. Jones, Michael J. Haley, Miriam H. Meadows, Grace E. Gregory, Cathal J. Hannan, Ana K. Simmons, Leoma D. Bere, Daniel G. Lewis, Pedro Oliveira, Miriam J. Smith, Andrew T. King, D. Gareth R. Evans, Pawel Paszek, David Brough (), Omar N. Pathmanaban () and Kevin N. Couper ()
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Adam P. Jones: The University of Manchester
Michael J. Haley: The University of Manchester
Miriam H. Meadows: The University of Manchester
Grace E. Gregory: University of Manchester
Cathal J. Hannan: University of Manchester
Ana K. Simmons: The University of Manchester
Leoma D. Bere: The University of Manchester
Daniel G. Lewis: University of Manchester
Pedro Oliveira: The Christie Hospital
Miriam J. Smith: University of Manchester
Andrew T. King: University of Manchester
D. Gareth R. Evans: University of Manchester
Pawel Paszek: The University of Manchester
David Brough: University of Manchester
Omar N. Pathmanaban: University of Manchester
Kevin N. Couper: The University of Manchester

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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 leucocyte 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 this study, to elucidate the complex immunological networks across VS, we performed imaging mass cytometry (IMC) on clinically annotated VS samples from NF2 SWN patients. We reveal the heterogeneity in neoplastic cell, myeloid cell and T cell populations that co-exist within VS, and that distinct myeloid cell and Schwann cell populations reside within varied spatial contextures across characteristic Antoni A and B histomorphic niches. Interestingly, T-cell populations co-localise with tumour-associated macrophages (TAMs) in Antoni A regions, seemingly limiting 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.

Date: 2025
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DOI: 10.1038/s41467-025-57586-z

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