Fig. 6: Immune remodeling in LTS patients is associated with future disease resurgence and defective immune function even in the absence of measurable disease. | Nature Communications

Fig. 6: Immune remodeling in LTS patients is associated with future disease resurgence and defective immune function even in the absence of measurable disease.

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

Fig. 6

a Correlation of malignant plasma cell fraction (CNV-based malignancy score) and degree of remodeling (mean DA-seq score). Spearman’s Rho is indicated. b Correlation between mean CXCR3 expression in CD8 + T cells and CNV-based malignancy score; Spearman’s Rho is indicated. c Correlation between the ratio of BM to PB CXCR3 + CD8 + T cells and BM cytological PC count. n(healthy) = 5, n(sust.CR) = 11, n(losingCR) = 11, n(ID) = 23. Spearman’s Rho is indicated. d Comparison of BM to PB ratio of CXCR3 + CD8 + T cells between sust.CR patients (n = 11) and patients losing CR (n = 11). The dashed line indicates the mean ratio of healthy controls. Significance was tested by unpaired Wilcoxon rank sum test. e Bar plot summarizing fractions of dissimilarity-based classification by the clinical group for CD8 + T cells (healthy n = 3; complete remission (CR) n = 6; non-CR n = 5). f Similar to (e) but for classical monocytes. g Distribution of the dissimilarity score by clinical group within CD8 + T compartment. Large dots indicate sample means. h Similar to (g) but for classical monocytes. (i–k) Boxplots of indicated gene/genesets. The dashed line indicates the mean module score of healthy control. Significance was tested by paired Wilcoxon rank-sum tests. l Fraction of CXCR3 + CD8 + T cells at ID, after induction, and high-dose melphalan and autologous stem cell transplantation (ASCT), n = 136 patients, significance determined by Wilcoxon signed-rank tests. Benjamini-Hochberg adjusted p-values are shown. m Correlation of CXCR3-positive T cells among paired samples from distinct therapy phases. Spearman’s Rho is indicated. n Study design scheme; created with BioRender.com. o Intracellular cytokines in T cells of LTS patients (n = 17) and controls (n = 10). Significance was tested by unpaired Wilcoxon rank sum test. If not stated otherwise, paired BM samples from 11 MM patients at ID and LTS, and 3 healthy controls were used. 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. Bar plots: Error bars indicate the standard error of the mean (SEM). Error bands in correlation graphs indicate a 95% confidence interval of best linear fit. All statistical tests were performed using a two-sided approach. Abbreviations: ID: initial diagnosis; LTS: long-term survival; CR: complete remission; BM: bone marrow; PB: peripheral blood.

Back to article page