The development of a complex tumour microenvironment by tumour cells and co-opted immune and stromal cells represent a key determinant of cancer progression and response to therapy. Moreover, the microenvironmental communication networks are instrumental in the development of metastasis.
Our research within the CCRCB in this area brings together interest in the cellular phenotypes, metabolism, proteolysis and cell to cell signalling that underpin the development of the tumour microenvironment. This includes:
- the contribution of the microvasculature and inflammatory cells on organ remodelling and metastasis (Branco)
- the immunomodulatory role of proteases and anti-proteases in tumour-associated inflammation (Small, Scott)
- impacts of epigenetics on the inflammatory microenvironment (LaBonte-Wilson)
- the effects of adipocytes and lipids on organelle biogenesis, membrane contact sites and metabolic adaptation in tumour cells (Evergren)
- microenvironmental impact on radiotherapy response including inflammatory-driven responses in normal tissues (Butterworth)
- anti-viral effects induced by innate sensing of DNA damage e.g. (cGAS-STING pathway
- drug deposition and immune cell targeting (Scott)
In exploring these questions, we employ a wide range of models that recapitulate aspects of the tumour and metastatic microenvironments, from complex physiological models such as patient-derived xenografts and syngeneic mouse models, to tumour explant cultures and cell-based metabolism methodologies. Effects on the tumour microenvironment are characterised using multi-scale approaches including subcellular imaging, high-throughput sequencing and informatics, whole animal imaging and proteomics.