Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer.
IF: 38.585
Cited by: 14


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.


Spatial Transcriptomics
kidney cancer
multi-regional sequencing
renal cell carcinoma
single-cell sequencing
tumor microenvironment

MeSH terms

Gene Expression Profiling
Carcinoma, Renal Cell
Kidney Neoplasms
Epithelial-Mesenchymal Transition
Tumor Microenvironment
Single-Cell Analysis


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