Fig. 5: Reciprocal cell-cell interactions promote immunosuppressive microenvironment. | Leukemia

Fig. 5: Reciprocal cell-cell interactions promote immunosuppressive microenvironment.

From: The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma

Fig. 5

A Exhaustion score. n = 3491 cells. ****p < 2.2e-16 by Wilcoxon test for all comparisons. B HAVCR2 expression. ****p < 2.2e-16 by Wilcoxon test for all comparisons. C Correlation between percentage of exhausted CAR-T cells and exhausted endogenous CD8 + T cells at M2D1. D Correlation between expression of an apoptosis gene signature in CAR-T cells and endogenous CD8 + T cells at M2D1. E Interaction count between CAR-T cells and endogenous T cells at M2D1. F Heatmap showing significant inferred cell-cell interactions between CAR-T cells and endogenous CD8 + T cells at M2D1. Only significant interactions (-log(pvalue) >3) are displayed. G TIM3 surface expression compared between CD8 + T cells from different timepoints and CAR-T cells generated by CITE-seq staining from the droplet-based scRNA-Seq dataset of bone marrow aspirates of 4 patients. n = 5158 cells. ****p = 5.9e-06 for M2D1, ****p = 3.5e-05 for M7D1 and *p = 0.026 for CAR-T cells by Wilcoxon test. H Boxplots showing persister scores depending on Galectin-9 plasma levels measured by ELISA. *p = 0.017 by Wilcoxon test. I Proportion of live T cells following pre-incubation with Gal9 in untransduced CD8 + T cells and CAR-T cells. p < 0.0001 by unpaired t-test. J Model illustrating the effect of GAL9 binding to TIM3 on CAR-T cell persistence and exhaustion. For A,G,H box plots show the median and the interquartile range, and whiskers extend to 1.5x the interquartile range.

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