Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer
Ruoyan Li, John R. Ferdinand, Kevin W. Loudon, Georgina S. Bowyer, Sean Laidlaw, Francesc Muyas, Lira Mamanova, Joana B. Neves, Liam Bolt, Eirini S. Fasouli, Andrew R.J. Lawson, Matthew D. Young, Yvette Hooks, Thomas R.W. Oliver, Timothy M. Butler, James N. Armitage, Tev Aho, Antony C.P. Riddick, Vincent Gnanapragasam, Sarah J. Welsh, Kerstin B. Meyer, Anne Y. Warren, Maxine G.B. Tran, Grant D. Stewart, Isidro Cortés-Ciriano, Sam Behjati, Menna R. Clatworthy, Peter J. Campbell, Sarah A. Teichmann, Thomas J. Mitchell
Abstract
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8+ T cell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target.
Datasets
1. Single-cell transcriptomic datasets of Renal cell carcinoma patients
Metadata
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Source data
https://cellxgene.cziscience.com/collections/f7cecffa-00b4-4560-a29a-8ad626b8ee08
Alias names
EGAD00001008781, EGAD00001008030, PMID36423636, PMC9767677
Cite this study
Li, R., Ferdinand, J.R., Loudon, K.W., Bowyer, G.S., Laidlaw, S., Muyas, F., Mamanova, L., Neves, J.B., Bolt, L., Fasouli, E.S. and Lawson, A.R., 2022. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell, 40(12), pp.1583-1599. https://doi.org/10.1016/j.ccell.2022.11.001
