RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.
Cancers evolve at a dynamic pace to adapt to immune pressure, colonize new niches, and evade therapy. Tracking these changes can help us improve diagnosis, better tailor therapies, and forestall recurrence, but it requires intensive monitoring beyond current clinical practice. The TRACERx project, set up in 2014, aims to integrate new technologies to study cancer evolution in up to 840 lung cancer patients. From analyzing longitudinal changes in tumor DNA, to studying how these changes can be detected in blood, and expanding into the characterization of tumor immune and tissue microenvironments, several groups work collaboratively to decipher patterns and mechanisms of evolution, with the aim of applying them to improve lung cancer care.
This collection showcases the work of the TRACERx consortium, and provides further resources to explore the data and analyses published up to date. Browse the most recent publications in Nature Research, previous work, as well as Comments and community-generated content.
Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer
A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.
TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.
Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer
Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution
Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.
Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions
Ghorani et al. use a multiomics approach to characterize the effect of tumour mutational burden on the differentiation of CD4 and CD8 T cell subpopulations in non-small cell lung cancer.
The first long-term study of how lung cancer evolves is revealing that therapies targeting multiple proteins in tumour cells could help to outpace the disease.
TRACERx is a multimillion pound project funded by Cancer Research UK. By mapping the differences between individual cancer cells in hundreds of patients, it aims to track lung cancer evolution in unprecedented detail.