Fig. 5

Overexpression of TIGIT and other DEGs in tumor cells associated with BA resistance. (A) UMAP plot of tumor cells. Each dot indicates an individual cell; color denotes patients (left) or treatment history (right). (B) Inferred copy number based on scRNA-seq data. B-cells from healthy donors are used as normal reference for CNV (Copy Number Variation) inference of malignant cells. (C) Bubble heatmap showing top DEGs across distinct groups. Dot size indicates fraction of expressing cells, colored according to normalized expression levels. (D-E) Box plots showing average expression of CD19 (D) and HLA class II genes (E) for single cells. P values determined by Mann-Whitney test. (F) Bubble heatmap showing expression of top upregulated genes in BA-relapsed tumor cells. (G-H) UMAP plots of single cells color-coded by the response to BA therapy (G) or by expression of individual genes TIGIT and LAG3 (H). (I) Box plot showing TIGIT expression in single B cells. P values determined by Mann-Whitney test. (J) Bubble heatmap showing expression of TIGIT in normal B cells from healthy donors (n = 2), and MCL cells from ibrutinib-sensitive (IBN-S, n = 4), ibrutinib-resistant (IBN-R, n = 17) or BA-resistant (BA-R, n = 6) parents. (K) TIGIT expression is acquired on the cell surface of MCL tumor cells from BA-relapsed patients (n = 4) compared to BA-sensitive patients (n = 3) (left panel). Histogram plots (right panels) show cell surface TIGIT expression on MCL tumor cells from two representative BA-relapsed patients