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, Researchers at the Wellcome Trust Sanger Institute 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. The researchers found 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. They 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.
Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer
Li R, Ferdinand JR, Loudon KW, Bowyer GS, Laidlaw S, Muyas F, Mamanova L, Neves JB, Bolt L, Fasouli ES, Lawson ARJ, Young MD, Hooks Y, Oliver TRW, Butler TM, Armitage JN, Aho T, Riddick ACP, Gnanapragasam V, Welsh SJ, Meyer KB, Warren AY, Tran MGB, Stewart GD, Cortés-Ciriano I, Behjati S, Clatworthy MR, Campbell PJ, Teichmann SA, Mitchell TJ. (2022) Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell [Epub ahead of print]. [article]