The TRACERx-study: cancer evolution and immune surveillance

Professor Charles Swanton (University College London, UK) leads the ambitious British TRACERx, a translational research project in 842 patients with non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), prostate cancer or melanoma, aimed at understanding the relationships between cancer chromosome evolution in metastases, immune evasion, adaptation and clinical outcome. What is the origin of lethal metastatic subclones? What are the mechanisms behind branched evolution and immune escape? Chromosomal instability drives loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus and is associated with poor outcome. HLA LOH occurs frequently and subclonally in NSCLC, is under positive selection, permissive for increased mutational burden and associated with elevated PD-L1. “The consequence of this heterogeneity is that each patient needs a unique therapy.”