Dr Alex Gordon-Weeks and colleagues have been awarded a Development Fund for their research into 'Targeting LOXL2 activity to alter extracellular matrix structure and promote immune checkpoint sensitivity in colorectal cancer'.
Colorectal cancers (CRCs) sensitive to immune checkpoint blockade therapy (ICB) has an excellent patient outcome, but less than 15% of CRCs are sensitive. Re-modelling the tumour microenvironment is a potential way to improve sensitivity. Tumours with excessive extracellular matrix (ECM) deposition and an absence of intra-tumoural T-cells are particularly insensitive to ICB and have poor outcomes. This project investigates whether ECM structure and composition is CRC subtype- and mutation-dependent by analysis of ECMs in genetically modified mouse models.
Colorectal cancer is the third most commonly diagnosed cancer worldwide, with an increasing prevalence across Europe. Surgery to remove the tumour and surrounding lymph nodes remains the mainstay treatment for colorectal cancer. Previous studies have found that the number of lymph nodes removed during surgery is a marker for improved survival. We have recently shown that lymph node yield is directly associated to the host-tumour immune response and cancer cell differentiation. It has been shown in other cancers that differentiated cells are more immunogenic than stem-like cells. This project seeks to mechanistically investigate the relationship between cancer cell differentiation and enhancement of the host-tumour immune response in colorectal cancer.
The CRUK Oxford Centre selected 12 projects to receive pump-priming funds. This unique scheme supports collaborative proof-of-concept research which is at too early a stage for major grant support but has significant translational potential.
Read about all the successful projects on the Oxford Cancer website.