Investigating the role of fibroblast ENPP1 expression in shaping the immune microenvironment of chromosomally unstable cancer

Cancer cells often have tangled, knotted DNA - this helps cancers grow, spread and resist anti-cancer treatments. This tangled DNA should help immune cells recognise and destroy the cancer, but cancer cells prevent this. One way in which cancers with tangled DNA prevent immune attack is by telling nearby normal cells, called fibroblasts, to make immune-inactivating proteins. My work suggests that one particular protein on fibroblasts protects cancers from immune cell attack - both by inactivating immune cells and by preventing immune cells from getting close to cancer cells. Fibroblasts do this by making the cancer "stiff", which makes it harder for immune cells to move around the cancer and destroy cancer cells. Understanding exactly how cancer cells tell fibroblasts to make this protein and what the consequences are for immune cells within the cancer is important because it could help us find new ways to attack these difficult-to-treat cancers.