Harnessing immune reactivity against the tumour microbiome

Understanding how the immune system recognizes pathogens guides us in the development of immune therapeutics for diseases such as cancer. So far, most work has focused on conventional T cells that need to be trained by the immune system to recognize and destroy malignant cells. This work has led to the development of successful and transformative immunotherapies currently available (anti-PD-1 inhibitors). However, half of all patients with therapy-sensitive tumour types do not respond to treatment, and in many other tumour types, including breast cancer, response rates are much lower. New treatments are therefore urgently needed. Here, we are focusing on a different population of immune cells, so-called gamma-delta T cells. These widely under-researched cells belong to the innate part of the immune system and are the first responders to pathogens, e.g., in case of bacterial or viral infections. These cells have gained some attention recently, as their specific biology makes them promising candidates for anti-cancer therapies. They can directly engage and kill cells they recognize as foreign or damaged, and they are very important to orchestrate other immune cells to set the body up for a strong immune reaction against the tumour. Gamma-delta T cells can be activated by cancer cells via certain metabolic products; however, they are up to 1000x better at being activated by bacterial products. Recently, evidence emerged that tumour cells, and in particular breast cancer cells, harbour intracellular, live bacteria, but the significance and function of these remain unknown. We want to explore if intratumoural bacteria in breast cancer lead to an activation of gamma-delta T cells and if we can harness the high activation potential of bacteria-derived products to trigger an immune reaction against the breast cancer cells which can lead to their eradication.