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. 2024 Feb 19;30(3):699–707. doi: 10.1038/s41591-024-02824-y

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© The Author(s) 2024

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a, Heat map of cluster-specific DEGs of monocyte clusters. b, Fold changes in the proportions of monocyte subclusters among myeloid cells among long-term responders (LR; n = 9), early progressors (EP; n = 9) and both (n = 18). c, UMAP and pseudotime trajectory initiated from early-activated classical monocytes toward either M1-skewed or M2-skewed route. d, The proportions of M1-skewed or M2-skewed monocytes among total monocytes among LR (n = 9) and EP (n = 9). e, Module scores for an M1-like gene set within the activated classical monocyte_2 subset in LR (n = 8) and EP (n = 9). f, Module scores for a gene set related to TAM among M2-skewed non-classical monocytes in LR (n = 9) and EP (n = 9). g, Ratio of classical to non-classical monocytes among LR (n = 7) and EP (n = 8). h, Module scores for the gene set upregulated by regorafenib in each monocyte cluster from LR (n = 9) and EP (n = 9). i, Module scores for the gene set upregulated in CSF1R_Up_from_L1000_CRISPR_KO_Consensus_Sigs in each monocyte cluster from LR (n = 9) and EP (n = 9). j, DEGs among total monocytes on C1D15 in LR (n = 9) versus EP (n = 10). Blue and yellow indicate genes significantly upregulated in LR and EP, respectively. k, Changes in the expression of NLRP3 and IL18 in LR (n = 9) and EP (n = 9). l, Module score for the NLRP3 inflammasome signaling pathway-related gene set in total monocytes of LR (n = 9) and EP (n = 9). Gating strategy of monocytes is shown in Extended Data Fig. 6b. *P < 0.05, according to a Wilcoxon signed-rank test for paired groups and two-tailed Mann–Whitney U-test for unpaired groups. Data are presented as mean ± s.d. In each box plot, the box represents the interquartile range, and whiskers represent minima and maxima. CM, classical monocyte; IM, indeterminate monocyte; KO, knockout; NCM, non-classical monocyte.