Fig. 6: Tumor immune microenvironment diversity and evolution associated with therapeutic resistance.

a A t-SNE overview of the immune cells that passed quality control. Cells are color-coded by the defined cell types. b The dynamics of CD8 T cell proportion during treatment in responders (Rs) and non-responders (NRs). p Values estimated by the linear regression model. c Differential CD8A (CD8 T cell marker) expression via bulk RNA-seq comparing ibrutinib responders (n = 15) and non-responders (n = 6) in a separate MCL patient cohort. p = 8.6 × 10⁻⁴ from two-sided Wilcoxon signed-rank test. d Additional patient cohort validation using flow cytometry showing a decreased CD8+ T cell population in ibrutinib-resistant patients compared to ibrutinib-sensitive patients (n = 65 samples, collected from 22 patients). In c and d, the line in the box is the median value. The bottom and top of the box are the 25th and 75th percentiles of the sample. The bottom and top of the whiskers are the minimum and maximum values of the sample. p Values correspond to two-side Wilcoxon Signed-rank Test. e Reverse correlation between CD8A expression or CD8+ T cell (%), and the tumor cell OXPHOS activity assessed by scRNA-seq. The Pearson correlation coefficient (r) is shown. The bounds of shape correspond to 95% confidence band for the regression line. p Values in b and e correspond to F test of linear regression model.