Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer

Authors: Ruoyan Li, John R. Ferdinand, Kevin W. Loudon, Georgina Bowyer, Sean Laidlaw, Francesc Muyas, Lira Mamanova, Joana B. Neves, Liam Bolt, Eirini S. Fasouli, Andrew Lawson, Matthew D. Young, Yvette Hooks, Thomas R. W. Oliver, Timothy Butler, James N. Armitage, Tev Aho, Antony C. P. Riddick, Vincent J. Gnanapragasam, Sarah J. Welsh, Kerstin B. Meyer, Anne Y. Warren, Maxine Tran, Grant D. Stewart, Isidro Cortés‐Ciriano, Sam Behjati, Menna R. Clatworthy, Peter J. Campbell, Sarah A. Teichmann, Thomas J. Mitchell - Cancer Cell 2022 cited by 253

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.