Multi-regional characterisation of renal cell carcinoma and microenvironment at single cell resolution
Li, R.; Ferdinand, J. R.; Loudon, K. W.; Bowyer, G. S.; Mamanova, L.; Neves, J. B.; Bolt, L.; Fasouli, E. S.; Lawson, A. R. J.; Young, M. D.; Hooks, Y.; Oliver, T. R. W.; Butler, T. M.; Armitage, J. N.; Aho, T.; Riddick, A. C. P.; Gnanapragasam, V.; Welsh, S. J.; Meyer, K. B.; Warren, A. Y.; Tran, M. G. B.; Stewart, G. D.; Behjati, S.; Clatworthy, M. R.; Campbell, P. J.; Teichmann, S. A.; Mitchell, T. J.
Show abstract
Tumour behaviour is dependent on the oncogenic properties of cancer cells and their multicellular interactions. These dependencies were examined through 270,000 single cell transcriptomes and 100 micro-dissected whole exomes obtained from 12 patients with kidney tumours. Tissue was sampled from multiple regions of tumour core, tumour-normal interface, normal surrounding tissues, and peripheral blood. We found the principal spatial location of CD8+ T cell clonotypes largely defined exhaustion state, with clonotypic heterogeneity not explained by somatic intra-tumoural heterogeneity. De novo mutation calling from single cell RNA sequencing data allows us to lineagetrace and infer clonality of cells. We discovered six meta-programmes that distinguish tumour cell function. An epithelial-mesenchymal transition meta-programme, enriched at the tumour-normal interface appears modulated through macrophage expressed IL1B, potentially forming a therapeutic target. Single sentence summaryKidney cancer evolution, prognosis and therapy are revealed by a single cell multi-regional study of the microenvironment.
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