Mapping CD8+ T cell infiltration and activity in the glioblastoma tumour microenvironment

Project Outline

Glioblastoma is the most common type of malignant brain tumour. They are highly aggressive tumours and are generally incurable, with a mean survival time following diagnosis of only 12-18 months.  Glioblastomas are viewed as cold tumours with limited T cell infiltration, but positive correlations have been identified between the number of proliferative CD8+ T cells within glioblastoma tumours and survival duration, indicating T cells can contribute towards tumour control. Nevertheless, T cell focussed immunotherapies effective in other tumour-types (such as anti-PDL1 treatment) have been largely ineffective in glioblastoma, for reasons that we still do not fully understand. As such, new treatments for glioblastoma are urgently needed. In this project, the student will investigate the pathways that influence T cell infiltration, compartmentalisation and activity within glioblastoma tumours. 

The student will work on an interdisciplinary programme of work where they will utilise cutting-edge high-dimensional imaging approaches combined with transcriptional profiling to analyse the location and phenotype of CD8+ T cell populations within the heterogeneous human glioblastoma tumour microenvironment (both within primary and recurrent tumours) and to interrogate the different neoplastic and immune cell populations that CD8+ T cell populations interact with within the tumour. 

The student will complement these studies with detailed mechanistic investigations using established and translationally relevant in vivo models of glioblastoma to understand the spatial and cellular features that repress T cell protective activities within the tumour microenvironment. This will include analyses of how cancer immunotherapies remodel the glioblastoma tumour landscape to influence CD8+ T cell infiltration, compartmentalisation, cellular communication and functionality within the tumour.  

Collectively, the project will provide training in cutting edge neuro-oncology methodologies and technologies, and will generate new insights into how to target T cell responses to treat glioblastoma. 

Applications for this project are now open. Please complete your application on The University of Manchester website.