RESEARCH
THEME 1
THE TUMOUR
The tumour microenvironment is continually evolving, in the process developing a complex, dynamic network of accessory cells - the stroma - which function to support a tumour whilst also putting strategies in place to hide from or suppress from the immune system.
These two are not mutually exclusive, and we aim to understand how and when in tumour evolution the stroma function to modify and potentially shut off any developing anti-tumour immune responses.
MECHANISMS OF CAF-MEDIATED IMMUNE SUPPRESSION
We are generating evidence to support the hypothesis that cancer associated fibroblasts of the stroma directly interact with and suppress tumour-reactive T cells. The diminshed number and functional capacity of tumour infiltrating T cells provides tumour cells with a "safe" site in which to thrive.
TECHNIQUES: Preclinical tumour models, 3D culture models, whole genome analysis, realtime confocal imaging, complex triple culture systems.
UNDERSTANDING STROMAL EVOLUTION
While we accept that stromal cells support the tumour, many of their pro-tumour functions are considered to occur "late" in development, however, there is a scarcity of knowledge as to how stromal populations arise or when in tumour evolution they acquire these traits. This project aims to systematically charactise stromal populations during tumour development from the very earliest stages through to metastasis.
TECHNIQUES: Preclinical tumour models, single cell technologies, 3D culture models, whole genome analysis, realtime confocal imaging, flow cytometry, functional assays.
DISSECTING STROMAL HETEROGENEITY
A major barrier to understanding CAF function within the tumour microenvironment is the lack of a universal CAF marker. CAFs dispaly remarkable heterogeneity as evidenced from the number of markers used to define them: PDGFRa, PDGFRb, aSMA, FAP, podoplanin, CD248, tenascin C... Do individual markers indicate the presence of distinct functional subsets, or are all populations essentially the same? We take an unbiased approach to determine heterogeneity during tumour progression at the population level and down to single cell resolution.
TECHNIQUES: Preclinical tumour models, single cell technologies, bioinformatics, whole genome analysis, functional assays.