Unlocking the Potential of Immunotherapies for NF2
NF2 BioSolutions UK & Europe Research Update
Grace Gregory’s Research
Grace Gregory is a second-year NF2 BioSolutions PhD student at the University of Manchester. Grace’s project focuses on the immune cells that invade the tumours that people with NF2-schwannomatosis can develop such as vestibular schwannoma and meningioma. The work runs in parallel with Adam Paul Jones’ PhD project and uses computational analyses, patient tumour samples and cells cultured in the lab to investigate the roles of immune cells in these tumours and how they may promote tumour growth. Grace and Adam’s projects are headed by the same supervisory team: Prof. Omar Pathmanaban, Prof. David Brough, Prof. Kevin Couper and Dr. Pawel Paszek.
Vestibular schwannoma (VS) are brain tumours found in NF2-schwannomatosis (NF2-SWN) patients and non-NF2-SWN sporadic patients. Using large, published data sets to compare the genes expressed in sporadic and NF2-SWN VS and high-resolution imaging to assess the tumour samples Gregory et al found strong similarities in the cell types, blood vessels, gene expression and inflammatory pathways of NF2-SWN and sporadic VS. This provides evidence for the use of sporadic samples to investigate NF2-SWN VS in the lab and a foundation for the hypothesis that immunotherapeutics may be equally effective in both sporadic and NF2-SWN VS tumours. The high abundance of immune cells noted in this study promotes these cells as potential immunotherapeutic avenues to modify the tumour immune microenvironment in order to reduce tumour growth in patients with either NF2-SWN or sporadic VS.
Adam Paul Jones’ Research
The advancement of treatments for individuals with NF2-related Schwannomatosis (NF2 SWN) has scarcely changed over the last few decades. Radiographic monitoring and tumour resection remain the main therapeutic interventions, with some patients benefiting from the off-label use of the chemotherapeutic agent Bevacizumab. However, the high tumour recurrence rates and disease burden associated with NF2 SWN, along with common post-surgical complications, highlight the need for investment in novel therapeutic targets for better management of NF2 SWN. Similarly to other solid tumours, NF2 SWN-related tumours have complex microenvironments that harbour various interactions between tumour cells, immune cells, and stromal cells. The spatial organisation of these cells within the tumour and the neighbourhoods they form determine various factors including tumour growth, anti-tumour immunity, and responsiveness to therapies. The aims of our research in Manchester are to define the dominant immunological pathways that persist in NF2 SWN tumours through various novel imaging and computational techniques and to validate these as robust therapeutic targets for use in patients.
The focus of my research is on understanding the immunological landscape of NF2 SWN-related vestibular schwannoma (VS). It is well known that these tumours have a strong inflammatory composition, with a vast proportion of these tumours being composed of macrophages. Using high-dimensional imaging technologies, we can fully characterise the various types of immune cells and their organisation within the tumour and infer how the positioning of these cells may consequentially affect tumour growth or immunity. I am particularly interested in understanding the function, or dysfunction, of T-cells in VS, and how we can therapeutically target them to enhance their biological function of tumour cell recognition and elimination. Advances in tumour immunotherapies have shown much success in various cancers including melanoma, colorectal and renal cell cancer, and we hope to highlight these established agents as novel interventions for the improvement of NF2 SWN patient lives.
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