Fig. 5: Bone marrow infiltration of inflammatory T cells is associated with myeloma burden and serves as an accessible biomarker for disease activity. | Nature Communications

Fig. 5: Bone marrow infiltration of inflammatory T cells is associated with myeloma burden and serves as an accessible biomarker for disease activity.

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

Fig. 5

a–d UMAP of CD8 + T cells with CXCR3 (a) and LAT1 (b) expression highlighted, split between healthy donors and ID patients; and highlighted ‘scRNA Remodeling Score’ (derived from scRNAseq data: healthy versus aberrant CD8 + T cells) (c) and ‘bulkRNA Remodeling Score’ (derived from RNAseq analysis of CXCR3 + versus CXCR3- CD8 + T cells) (d). e Multiplex immunofluorescence of MUM1 (plasma cells), CXCR3, and LAT1 in representative BM area of an MM patient (arrows indicated examples of LAT1 and CXCR3 co-expression on T cells). f Left, CXCR3 mean expression intensity (MEI) on BM CD8 T cells of 33 MM, 12 B Non-Hodgkin lymphoma, and 11 MDS patients. Benjamini-Hochberg adjusted p-values from unpaired two-sided Wilcoxon rank-sum tests are shown; Right, Spearman correlation of fraction of CXCR3 + T cells (threshold: > 10 T cells) with tumor burden (MUM1 + plasma cells in the BM) (n = 40). g UMAP of CD8 + T cells with highlighted velocities (arrows), dissimilarity score (yellow), and imputed CXCR3 and LAT1 expression. h Fraction of CXCR3 + CD8 + T cells in PB (n = 50) and BM (n = 50) in patients with low/intermediate (< 50% plasma cells, blue) or high tumor burden (> 50% plasma cells, green). Significance was tested by a two-sided unpaired Wilcoxon rank sum test. i Hierarchical clustering CD8 + T cells (+/− CXCR3) from BM and PB (n = 3) by clonotypes of T cell receptor (TCR) repertoire using the Jaccard index of repertoire similarity. j Clonotype tracking by representative CDR3 amino acid sequence of shared clonotypes between the top 10 most abundant TCR clonotypes from CXCR3 + (top row) and CXCR3- (bottom row) PB CD8 + T cells across T cell subsets in PB and BM. Two representative patients are shown (see also Supplementary Fig. 6). Amino acid clonotype sequences are indicated. Bar plots: Error bars indicate the standard error of the mean (SEM). Abbreviations: FACS: fluorescence-activated cell sorting; BM: bone marrow; PB: peripheral blood; IF: immunofluorescence; MEI: mean expression intensity; MDS: myelodysplastic syndrome; ASCT: autologous stem cell transplantation; MFI: mean fluorescence intensity; TCR: T cell receptor.

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