The success of immune checkpoint inhibitors in cancer therapy illustrates the inherent ability of the immune system to control and occasionally eliminate advanced tumours. However, a majority of patients still do not respond to immunotherapy or lack long-term responses due to a poor tumour infiltration of immune cells or development of tumour resistance respectively. Our team studies how localised radiotherapy can be used to trigger new immune responses that promotes tumour immune cell infiltration rendering the host susceptible to immune checkpoint inhibitors.
As solid tumours evolve, they shape their microenvironment to evade attacks from the immune system by generating suppressive barriers and subverting homeostatic mechanisms. Our team investigates how radiotherapy modulates these processes and how we can tailor combined radiotherapy/immunotherapy to exert maximum anti-tumour effect and counteract tumour immune resistance.
By developing mouse tumour models that accurately mimic the molecular events that occur following different radiotherapy regimens, we are able to evaluate the mechanisms and pathways that dictate the radiation-induced immune response. Currently, we are focusing on how radiotherapy modulates purinergic and adenosinergic signalling in the tumour microenvironment.
Further, in collaboration with clinicians from the Royal Marsden NHS Foundation Trust, we analyse tumour samples from cancer patients treated with radioimmunotherapy to map the tumour immune landscape and correlate it with clinical parameters in response to therapy. This translational approach allows us to identify predictive biomarkers and actionable markers that can be targeted to optimize the immunogenic effect of radiotherapy and its synergy with immune checkpoint blockade.
The ultimate goal of our research is to develop novel combination therapies that could improve the treatment of patients with advanced metastatic cancer.