Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for 1.8 million deaths globally in 2020. This is largely due to the fact that lung tumours change over time by acquiring new mutations, making treatment difficult. This is called tumour evolution, and through an increased understanding of this process we will be able to better treat patients by tailoring treatments to individuals. TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective clinical trial that aims to do just that by following over 800 lung cancer patients starting from diagnosis through surgery and relapse. This study has uncovered that the more diverse a patient’s tumour at time of surgery, the worse their outcome. Diversity can be thought of as the number of tumour cell lineages that have evolved to result in the mass detected at diagnosis. From Darwinian principles, we know the environment plays a large part in shaping the evolution of species. This project aimed to increase our understanding of how the immune system acts as an environmental force to shape the evolution of lung tumours.
At the Francis Crick Institute, with the support of the European Commission and Bristol Myers Squibb, we have developed a method to look at lung cancer cells in their native environment in unprecedented detail. We have used this method to understand whether the immune system is activated or repressed and how it changes over time. We were also able to integrate detailed clinical and genetic information to understand the relationship between particular subtypes of lung cancer, lung cancer diversity, and the corresponding immune response. The outputs of this work will help inform the rational design of new therapies with the goal of activating the immune system to ultimately improve lung cancer patient outcomes.
