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

Li, Ruoyan; Ferdinand, John R; Loudon, Kevin W; Bowyer, Georgina S; Laidlaw, Sean; Muyas, Francesc; Mamanova, Lira; ... Mitchell, Thomas J; + view all (2022) Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell , 40 (12) 1583-1599.e10. 10.1016/j.ccell.2022.11.001. Green open access

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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.

Type: Article
Title: Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2022.11.001
Publisher version: https://doi.org/10.1016/j.ccell.2022.11.001
Language: English
Additional information: © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Renal cell carcinoma, kidney cancer, tumor microenvironment, single-cell sequencing, multi-regional sequencing, pseudocapsule, IL1B
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10169006
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