Figure 2.
SE largely overrides the transcriptional effect of romidepsin in malignant T cells. (A-B) Representative flow cytometric plots (A; SS8) and quantification (B) of percentage of viable malignant cells from PBMCs of 10 patients with SS (SS4, SS7, SS8, SS10, SS11, SS12, SS13, SS15, SS16, and SS17) treated with 2 nM romidepsin for 72 hours in the presence (SE) or absence (PBS) of SE. Red triangle shows the PBMCs of a patient with SS, which did not respond to romidepsin treatment. Statistical significance was assessed by ordinary 1-way ANOVA followed by Tukey multiple comparison test. ∗∗P < .01; ∗∗∗P < .0005. (C-E) Integrated uniform manifold approximation and projection (UMAP) from the 4 sample conditions (DMSO, romidepsin, SE, and SE + romidepsin) based on both mRNA and surface protein expression using totalVI colored by cell types (C), TCRβ CDR3 clonotype (D), and sample culture conditions (E; SS17). (F) Heatmap showing relative mean expression of malignant T cells after 36 hours treatment with romidepsin in the presence or absence of SE in SS17. Genes were selected based on differential expression between treatment and PBS control with a false discovery rate (FDR) <0.05 and a log2 fold change >0.5 or <−0.5 among any of the 3 treatments, yielding 574 genes in total. (G) Gene-set enrichment analysis (GSEA) of immune system pathways included in the Reactome database comparing 3 treatment conditions after 36 hours of culture (SS17): romidepsin (Ro), SE, and SE + romidepsin with PBS-treated control. Plot shows top 15 pathways from each comparison based on highest absolute normalized enrichment scores (NES) having a q-value <0.05. Other pathways are included in supplemental Figure 2E. (H) Transcription factor activity analysis using DoRothEA transcription factor signatures comparing 3 treatment conditions after 36 hours of culture (SS17): romidepsin, SE, and SE + romidepsin with PBS-treated control. Plot shows top 10 differentially activated transcription factors from each comparison based on highest absolute log2 fold change having an FDR <0.05. DMSO, dimethyl sulfoxide; mRNA, messenger RNA; NK cells, natural killer cells.

SE largely overrides the transcriptional effect of romidepsin in malignant T cells. (A-B) Representative flow cytometric plots (A; SS8) and quantification (B) of percentage of viable malignant cells from PBMCs of 10 patients with SS (SS4, SS7, SS8, SS10, SS11, SS12, SS13, SS15, SS16, and SS17) treated with 2 nM romidepsin for 72 hours in the presence (SE) or absence (PBS) of SE. Red triangle shows the PBMCs of a patient with SS, which did not respond to romidepsin treatment. Statistical significance was assessed by ordinary 1-way ANOVA followed by Tukey multiple comparison test. ∗∗P < .01; ∗∗∗P < .0005. (C-E) Integrated uniform manifold approximation and projection (UMAP) from the 4 sample conditions (DMSO, romidepsin, SE, and SE + romidepsin) based on both mRNA and surface protein expression using totalVI colored by cell types (C), TCRβ CDR3 clonotype (D), and sample culture conditions (E; SS17). (F) Heatmap showing relative mean expression of malignant T cells after 36 hours treatment with romidepsin in the presence or absence of SE in SS17. Genes were selected based on differential expression between treatment and PBS control with a false discovery rate (FDR) <0.05 and a log2 fold change >0.5 or <−0.5 among any of the 3 treatments, yielding 574 genes in total. (G) Gene-set enrichment analysis (GSEA) of immune system pathways included in the Reactome database comparing 3 treatment conditions after 36 hours of culture (SS17): romidepsin (Ro), SE, and SE + romidepsin with PBS-treated control. Plot shows top 15 pathways from each comparison based on highest absolute normalized enrichment scores (NES) having a q-value <0.05. Other pathways are included in supplemental Figure 2E. (H) Transcription factor activity analysis using DoRothEA transcription factor signatures comparing 3 treatment conditions after 36 hours of culture (SS17): romidepsin, SE, and SE + romidepsin with PBS-treated control. Plot shows top 10 differentially activated transcription factors from each comparison based on highest absolute log2 fold change having an FDR <0.05. DMSO, dimethyl sulfoxide; mRNA, messenger RNA; NK cells, natural killer cells.

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