Fig. 6: Identification of IL1β+ monocyte transcriptional signature associated with lack of response to PD-1 blockade. | Nature Communications

Fig. 6: Identification of IL1β+ monocyte transcriptional signature associated with lack of response to PD-1 blockade.

From: Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma

Fig. 6

a Differential expression analysis of response-related Cluster 0 transcripts in patients with relapsed/refractory (R/R) cHL who achieved a complete response (CR) or progressed on PD-1 blockade (PD). A two-sided permutation test, adjusted for multiple comparisons (adj p < 0.1, fold change > 1.5) was used to filter the differentially expressed Cluster 0 genes in patients who achieved a CR or progressed on therapy at C4D1. The top 50 of 368 differentially expressed genes are shown for patients by response at C4D1 and baseline C1D1. b Pathway enrichment analysis of response-related differentially expressed genes in Cluster 0 using Molecular Signatures Database (MSigDB) gene sets: CP:REACTOME: Reactome gene sets; CP:WIKIPATHWAYS: WikiPathways gene sets; and C7: Immunologic gene sets. Gene Ratio (x-axis) represents the number of genes in the AUCell signature over the total number of genes in a given gene set; FDR significant < 0.05; Count represents the number of genes in the overlap between the AUCell gene signature and given gene set. c AUCell signature score in circulating Cluster 0 monocytes from healthy donors (HD) and patients with newly diagnosed cHL (ND) or R/R cHL at C1D1 and C4D1 at the single-cell (upper panel: HD n = 73 cells; ND n = 8266 cells; CR C1D1 n = 3942 cells; PD C1D1 n = 2390 cells; CR C4D1 n = 5403 cells; PD C4D1 n = 4335 cells) and per-patient (lower panel: HD n = 12 samples; ND n = 11 samples; CR C1D1 n = 9 samples; PD C1D1 n = 6 samples; CR C4D1 n = 9 samples; PD C4D1 n = 5 samples) levels. d AUCell signature score in all circulating monocytes from HDs and patients with cHL at the single-cell (upper panel: HD n = 28,001 cells; ND n = 20,633 cells; CR C1D1 n = 16,851 cells; PD C1D1 n = 7464 cells; CR C4D1 n = 17,343 cells; PD C4D1 n = 10,999 cells) and per-patient (lower panel: HD n = 13 samples; ND n = 11 samples; CR C1D1 n = 9 samples; PD C1D1 n = 6 samples; CR C4D1 n = 9 samples; PD C4D1 n = 5 samples) levels. e AUCell signature score in all circulating monocytes from patients with metastatic urothelial carcinoma (mUC) (Yuen et al. Nat Med 26, 693-698 (2020)) at baseline (C1D1), stratified by the subsequent response to PD-L1 blockade, at the single-cell (upper panel: Responders n = 3718 cells, Non-responders n = 4134 cells) and per-patient (lower panel: Responders n = 5 samples, Non-responders n = 5 samples) levels. c–e A one-sided Wilcoxon rank-sum test was used to assess the distributions of AUCell gene signature scores between HD and ND, as well as between CR and PD at C1D1 and C4D1, at both the single-cell and per-patient levels. c–e (upper panel) All violin plots generated in R illustrate the data distribution with kernel density estimation. Plots display the 25th and 75th percentiles (lower and upper hinges) and median values. The width of the violin at different points reflects the density of the data. (upper panels) All box plots display the 25th and 75th percentiles (lower and upper hinges), median values, and whiskers. The whiskers extend from the hinges to the largest/smallest values within 1.5 times the interquartile range (IQR) from the hinge. Data points beyond the end of the whiskers are plotted individually. Source data are provided as a Source Data file.

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