Investigating the role of fibroblast-like cells in shaping the glioblastoma tumour microenvironment (360G-Wellcome-337235_Z_25_Z)

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant cancers, with a poor prognosis. Treatment resistance is largely attributed to the tumour’s highly heterogeneous microenvironment. GBM consists of multiple neoplastic cell subtypes, each with distinct phenotypes and associations with extracellular matrix (ECM) remodelling, immune cell recruitment, and hypoxic gradients, creating specialised histomorphic niches. The mechanisms by which these niches arise, however, remain unclear. Increasing evidence from other solid tumours highlights the role of stromal fibroblast-like populations in driving ECM remodelling, tumour progression, and immune evasion, yet their contribution in GBM is poorly understood. This project aims to define the mechanisms underpinning the extensive ECM remodelling in GBM and investigate how this process shapes immune cell polarisation within the tumour microenvironment. We will employ a combination of in vivo, in vitro, and in silico approaches to characterise the cellular drivers of ECM remodelling and how this may contribute to immunosuppression within the tumour.