Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma

Ritzmann, Timothy; Lourdusamy, Anbarasu; Jackson, Andrew; Storer, Lisa; Donson, Andrew; Griesinger, Andrea; Foreman, Nicholas; Rogers, Hazel; Grundy, Richard

Abstract

Ependymoma is the third commonest childhood brain tumour. Relapse is frequent, often fatal and current therapeutic strategies are inadequate. Previous ependymoma research describes an immunosuppressive environment with T-cell exhaustion, indicating a lack of response to T-cell directed immunotherapy. Understanding the immune microenvironment is therefore critical. We present a computational analysis of ependymoma, gene expression derived, immune profiles. Using 465 ependymoma samples from gene expression datasets (GSE64415, GSE50385, GSE100240) and two RNA-seq databases from UK ependymomas, we applied bulk tumour deconvolution methods (CIBERSORT and xCell) to infer immune cell populations. Additionally, we measured checkpoint blockade related mRNAs and used immunohistochemistry to investigate cell populations in ependymoma sections. CIBERSORT indicated high proportions of M2-like macrophages and smaller proportions of activated natural killer (NK) cells, T follicular helper cells, CD4+ memory T-cells and B-cells. xCell overlapped with the M2-like macrophage and CD4+ memory T-cell signatures seen in CIBERSORT. On immunohistochemistry, T and B cells were scarce, with small numbers of CD8+, CD4+ and CD20+ cells in the parenchyma but greater numbers in surrounding regions. CD68 was more highly expressed in the parenchyma. Analysis of nine checkpoint ligands and receptors demonstrated only the TIM3/GAL9 combination was reliably detectable. GAL9 is implicated in tumour interactions with T-cells and macrophages elsewhere, possibly contributing to poorer outcomes. Our study supports the presence of myeloid cells being leading contributors to the ependymoma immune microenvironment. Further work will delineate the extent of myeloid contribution to immunosuppression across molecular subtypes. Modulation of tumour immunity may contribute to better clinical outcomes.

Citation

Ritzmann, T., Lourdusamy, A., Jackson, A., Storer, L., Donson, A., Griesinger, A., …Grundy, R. (2020). Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma. Neuro-Oncology, 22(Supplement 3), iii312. https://doi.org/10.1093/neuonc/noaa222.160

• Journal Article Type: Meeting Abstract
• Acceptance Date: Mar 25, 2020
• Online Publication Date: Dec 4, 2020
• Publication Date: Dec 4, 2020
• Deposit Date: Jan 18, 2021
• Publicly Available Date: Jan 19, 2021
• Journal: Neuro-Oncology
• Print ISSN: 1522-8517
• Electronic ISSN: 1523-5866
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Not Peer Reviewed
• Volume: 22
• Issue: Supplement 3
• Pages: iii312
• DOI: https://doi.org/10.1093/neuonc/noaa222.160
• Keywords: Cancer Research; Oncology; Clinical Neurology
• Public URL: https://nottingham-repository.worktribe.com/output/5242603
• Publisher URL: https://academic.oup.com/neuro-oncology/article/22/Supplement_3/iii312/6018544