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. 2021 Jul 21;596(7870):126–132. doi: 10.1038/s41586-021-03752-4

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© The Author(s) 2021, corrected publication 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 5 — a, A heat map shows the top differential genes, ranked by average fold change, for each refined CD8 T cell cluster. 5,000 cells (or all cells in the cluster if cluster size <5000 cells) were randomly sampled from each cluster for visualization (n = 16 patients). b, Violin plots show the log10 expression of the TRM-defining genes, ITGAE (top) and ZNF683 (HOBIT, middle), and a TRM gene-set score (bottom) for each CD8 T cell cluster. The dashed line indicates the mean expression of the respective gene or gene-set score among all CD8 T cells. Because the proliferating cluster is driven by proliferation-associated genes and represents mixed cell types, this cluster was not shown in the plot. c, 2D UMAP red-scale projection of canonical T cell subset marker genes, cell subset selective genes, and immune checkpoints on CD8 T cell subsets. d, A heat map shows the proportion of each refined CD8 T cell cluster (Fig. 2b) that is found within each global UMAP T cell cluster (Fig. 1b). This enables visualization of the “parent” cluster for the refined CD8 T cell clusters. e, A violin plot shows the exhaustion gene-set score, comprised of a published exhaustion gene list (Supplementary Data 2.2), for each refined CD8 T cell cluster. The dashed line shows the mean exhaustion gene-set score among all CD8 T cells. Because the proliferating cluster is driven by proliferation-associated genes and represents mixed cell types, this cluster was not shown in the plot. f, CD8⁺ T cell clonotypic cluster composition. The top 50 CD8⁺ TCR clonotypes in the tumour are shown for each patient, and the proportion of each clonotype that was found within each cluster is designated by the colour code.