The College has launched a new blog series – called Service Spotlight – highlighting services that have made impressive changes in their practice that improve quality and/or patient safety. This is the first blog in the series, highlighting the Liverpool Ophthalmic Pathology Service and its associated Research Team.
Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development.
Figueiredo CR1,2, Kalirai H1, Sacco JJ1,3, Azevedo RA4, Duckworth A1, Slupsky JR1, Coulson JM5, Coupland SE1,6.
We show that BAP1 loss is correlated with upregulation of several genes associated with suppressive immune responses, some of which build an immune suppressive axis, including HLA-DR, CD38, and CD74. Further, single-cell analysis of pUM by mass cytometry confirmed the expression of these and other markers revealing important functions of infiltrating immune cells in UM, most being a regulatory CD8+ T lymphocytes and tumour associated macrophages (TAMs). Transcriptomic analysis of hepatic mUM revealed similar immune profiles to pUM with BAP1 loss, including the expression of IDO1. At the protein level, we observed TAMs and TILs entrapped within peritumoral fibrotic areas surrounding mUM, with increased expression of IDO1, PD-L1 and β-catenin (CTNNB1), suggesting tumour-driven immune exclusion and hence the immunotherapy resistance. These findings aid the understanding of how the immune response is organised in BAP1- mUM, which will further enable functional validation of detected biomarkers and the development of focused immunotherapeutic approaches. This article is protected by copyright. All rights reserved.
Full article https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.5384
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