Constructing an evolutionary atlas of the immune landscape in lung cancer

ended

The immune system imposes a continuous selective pressure that influences the evolutionary trajectories of tumour cell populations. The interplay between evolving genetics of tumour cells and the corresponding immune response is poorly understood. A deeper understanding of tumour microenvironmental constraints upon cancer evolution may define an evolutionary rulebook and help to inform the rational and personalized design of combination immunotherapies for the treatment of cancer. In this study, we aim to integrate detailed genomic information from the TRACERx lung cancer cohort (TRAcking lung Cancer Evolution through therapy (Rx), a multiregion longitudinal study aiming to study >5000 tumour regions from 842 patients) with highly multiplexed tumour microenvironment imaging mass cytometry data in order to decipher the dynamics of distinct microenvironmental cell types during the disease course and tentatively begin to construct the rulebook of cancer. We will characterize how the tumour genome and microenvironment evolves throughout the disease course by analyzing multiregion tumour samples taken at time of surgery, relapse and death through the fast-autopsy PEACE study (Posthumous Evaluation of Advanced Cancer Environment). Successful completion of these aims will generate the most complete understanding of the lung tumour microenvironment to date within the contexture of the evolving tumour genome. This knowledge will ultimately inform the design of innovative precision medicine strategies in lung cancer.