Fig. 5. Murine PTCL-NOSSmarcb1− recapitulates key features of human tumors.
A UMAP plot showing 24 clusters of the integrated scRNA-seq dataset from two control spleen samples (WT) and two PTCL-NOSSmarcb1− tumor samples. B Relative abundance of different cell types in murine WT spleens (left), PTCL spleens (middle), and human tumors (right; NB: in order to ensure comparability, the stromal cells were removed before quantification). The pie charts in the lower part show the ratio between B-cells and myeloid cells. C Multiplex immunofluorescence (IF) images of FFPE sections of murine PTCL-NOSSmarcb1− and control spleen samples (WT: upper panels; tumor: lower panels). For better visualization, the white boxed areas (a to f) are enlarged (2.5x; scale bar = 100 µm). DAPI (gray) provides a nuclear counterstain, Ezh2 (yellow) defines malignant cells (Ezh2hi), B220 (blue) is used as a pan B-cell marker (B220+), and Ly6g (pink) as a marker for neutrophils (Ly6g+). D Quantitative analysis of IF images from (C). Four representative regions of interest (ROIs; size: 1500 × 1500 µm) were selected and analyzed for mouse WT and Tumor samples. A Wilcoxon-Mann-Whitney test was calculated to determine if there are differences between WT and Tumor samples for all comparisons (*p = 0.0286). Boxplot settings: middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ±1.5 * IQR. E The heatmap shows the overlap between cluster-specific DEG lists and the cancer hallmark metaprograms. F Signature plots of the programs Cycling, MYC, EMT and Stress in cells from WT (left) and tumor (right) samples. G A split violin plot (left/gray half: WT; right/black half: tumor) illustrates the increase in T-cell exhaustion features (Exhaust.) with a simultaneous decrease in NK cytotoxicity (Cytotox.) markers (e.g., Ncr1/NKp46) as well as infiltration of immunosuppressive myeloid cells in tumor versus WT samples. Source data of B and D are provided as a Source Data file. B Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.