Abstract
Background: Meningiomas are the most common primary intracranial tumours, ranging from benign to highly aggressive forms. While surgery is effective for low-grade meningiomas, certain grade 1 tumours, as well as grade 2, 3, and recurrent cases are more aggressive and require new therapeutic approaches. Immunotherapy shows promise, however, the role of tumour microenvironment (TME), particularly tumour-associated macrophages (TAMs), in meningiomas remains poorly understood, especially concerning genomic alterations. Aims: To investigate the immune landscape of meningiomas classified by grades, genotypes and methylation classes (MCs), and to elucidate the role of the TAMs in meningioma progression utilising a patient-derived 3D co-culture model.Methods: Multiplex immunohistochemistry and bulk RNA sequencing were used to characterise the TME in genetically stratified meningioma tissues and their matched 3D spheroid models. Comparative analyses of immune cell infiltration were conducted across parental tissues, 2D monolayer cultures, and 3D models. In co-culture experiments, M2-polarised macrophages or microglia derived from peripheral blood mononuclear cells were introduced to patient-matched 3D models to investigate tumour cell behaviour in the presence of immune cells. Quantitative PCR was performed to examine macrophage-related cytokine expression and explore the molecular mechanism of tumour-immune interactions.Results: Distinct differences in the TME were observed across various genotypes and MCs. Notably, benign NF2-mutant and MC ben-1 tumours exhibited higher proportions of microglia and M2-like microglia, whereas aggressive MC mal tumours showed an increased presence of macrophages and M2-like macrophages. The 3D models closely resembled the TME of parental tissues, providing a more accurate platform than 2D. In co-cultures, M2-polarised immune cells infiltrated tumour spheroids, promoting proliferation while inhibiting invasion, with tumour cells displaying elevated IL-6 in their presence. Conclusion: The study demonstrates that the TME in meningiomas varies with genotype and molecular subtype. The patient-derived 3D model effectively reflects the immune landscape of parental tissues, providing valuable insights for developing novel immunotherapeutic strategies to improve patient outcomes.
Awarding Institution(s)
University of Plymouth
Supervisor
Juri Na, Gyorgy Fejer, Claire Adams, Oliver Hanemann
Document Type
Thesis
Publication Date
2025
Embargo Period
2025-10-16
Deposit Date
October 2025
Additional Links
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Zhang, T. (2025) Exploring the immune landscape of the tumour microenvironment in meningiomas and the role of immune infiltration in meningioma models. Thesis. University of Plymouth. Available at: https://doi.org/10.24382/ymrr-8632
