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. 2021 Nov 2;126(2):247–258. doi: 10.1038/s41416-021-01599-0

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© The Author(s) 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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Fig. 3 — a Panels 1 and 2 = Gene signatures predicting acquired (panel 1) and innate (panel 2) immune cell infiltrating populations in DDIR-negative (left) and DDIR-positive (right) tumours; ex T cells exhausted T cells, DC dendritic cells, NK natural killer cells. Panel 3 = macrophage polarisation. Panel 4 = Immune signalling pathways identified as active in DDIR assay-positive and -negative tumours. Panel 5 = Expression of immune-checkpoint genes in DDIR-negative and positive tumours. DDIR status and RCB score (0–3) is indicated on x axis for all 46 samples. *P < 0.05; **P < 0.01; ***P < 0.001, unpaired t test. b Panel 1 = Gene signatures derived from clara^T analysis and reported to predict response to immune-checkpoint blockade, as well as the DDIR assay [8, 28–30, 58–60]. Panel 2 = Gene signatures derived from claraT analysis and reported to predict resistance to ICB in DDIR-negative and -positive tumours [27, 31–33]. Panel 3 = Gene signatures associated with increased angiogenic signalling or response to anti-angiogenic agents [34–36, 61]. Panel 4 = Gene signatures associated with increased EMT signalling [26, 37–39, 62]. DDIR status and RC score (0–3) is indicated on x axis for all 46 samples. *P < 0.05; **P < 0.01; ***P < 0.001, unpaired t test. c Correlations of gene signatures predicting angiogenic, EMT or immune signalling. Signatures predicting angiogenic or EMT signalling negatively correlated with those predicting immune signalling. Significance of correlation is shown using size, red indicates a positive correlation and blue negative correlation (gene signature references as for Fig. 4b).