Fig. 4: An inflammatory circuit underlies immune remodeling during active disease and long-term survival. | Nature Communications

Fig. 4: An inflammatory circuit underlies immune remodeling during active disease and long-term survival.

From: Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy

Fig. 4

a Significantly enriched gene sets in aberrant cell types at ID versus healthy controls. Selected gene sets are shown. Benjamini-Hochberg adjusted p-values are encoded by dot size, colors represent normalized enrichment scores (NES). Stars mark significant enrichment of the selected gene sets. b Left, correlation between indicated module score and dissimilarity score in CD14 + monocytes. Cell density is color-coded. Spearman’s Rho and the significance level of correlation are indicated. Right, distribution of indicated module score by clinical group. Benjamini-Hochberg adjusted p-values from unpaired (Healthy/ID, Healthy/LTS) and paired (ID/LTS) two-sided Wilcoxon rank-sum tests are shown. c Boxplots of indicated module score (see b) in CD14 + monocytes split by clinical group and cell state prediction (n(ID/healthy) = 9, all other n = 11). The dashed line represents the mean expression of healthy controls. Significance was tested by paired two-sided Wilcoxon rank-sum tests. d Mean CXCL8 expression at ID and LTS per patient. e Boxplots of mean CXCL8 expression in CD14 + monocytes split by clinical group and cell state prediction. The dashed line represents the mean expression of healthy controls. Significance was tested by paired two-sided Wilcoxon rank-sum tests. f NK cytotoxicity module score in NK cell subsets. Benjamini-Hochberg adjusted p-values from unpaired (Healthy/ID, Healthy/LTS) and paired (ID/LTS) two-sided Wilcoxon rank-sum tests are shown. g Predicted the number of interactions between plasma cells and immune cells at ID using CellPhoneDB. h Mean interferon-gamma (IFNG) expression at ID and LTS per patient. i, j Boxplots of IFNG (i) and CXCR3 (j) expression in CD8 + T cells split by clinical group and cell state prediction (n per group/condition = 11). The dashed line represents the mean expression of healthy controls. Significance was tested by paired two-sided Wilcoxon rank-sum tests. If not stated otherwise, paired human BM samples from 11 MM patients at ID, LTS, and 3 healthy controls were used for comparison. Abbreviations: CD14/CD16_M: CD14 + /CD16 + monocytes; cDC: conventional dendritic cells; pDC: plasmacytoid dendritic cells; CD4/CD8_T: CD4 + /CD8 + T cells; NK: natural killer cells. Box plots: center line, median; box limits, first and third quartile; whiskers, smallest/largest value no further than 1.5*IQR from the corresponding hinge.

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