Stone, Thomas J;
Pickles, Jessica C;
Ogunbiyi, Olumide;
Yasin, Shireena A;
Taylor, Catherine A;
Ahmed, Saira W;
Chalker, Jane;
... Jacques, Thomas S; + view all
(2025)
The tumour microenvironment of pilocytic astrocytoma evolves over time via enrichment for microglia.
Acta Neuropathologica Communications
, 13
, Article 30. 10.1186/s40478-024-01922-9.
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Abstract
Pilocytic astrocytoma (PA) is the commonest low-grade tumour affecting children and is frequently experienced as a chronic disease associated with extended treatment, periods of regrowth, and long-term disability. This contrasts with the view of PA as a benign tumour with positive clinical outcomes and raises the fundamental question of biologically driven change over time within these tumours, which will impact diagnosis, stratification, and management. To investigate the molecular, cellular, and pathological stability of PA we performed RNA sequencing, methylation array profiling, immunohistochemistry, and targeted panel DNA sequencing on a cohort of 15 PA patients with matched primary/longitudinal samples at a mean sampling interval of 2.7 years. Through pairwise analysis of primary versus longitudinal tumour samples we identified changes to immune-related pathways within the expression and methylation profiles of longitudinal PA. Further interrogation of these changes revealed an enrichment over time for microglial cell populations, which was validated by immunohistochemistry against common monocyte/microglial markers. Moreover, immunohistochemical characterisation revealed concurrent increases in the expression of M2-like and anti-inflammatory markers. Microglial enrichments were consistent across the cohort and were not adequately explained by a range of potential confounders, including receipt of adjuvant therapy. Taken together, these data challenge the idea of pilocytic astrocytoma as a static entity and indicate that they consistently accumulate microglia over time, potentially co-opting the immune microenvironment towards an anti-inflammatory phenotype that may affect the natural course and treatment response of the tumours.
| Type: | Article |
|---|---|
| Title: | The tumour microenvironment of pilocytic astrocytoma evolves over time via enrichment for microglia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s40478-024-01922-9 |
| Publisher version: | https://doi.org/10.1186/s40478-024-01922-9 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Low-grade glioma, Pilocytic astrocytoma, Microglia, Immune microenvironment. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10214534 |
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