Figure 5.
CDP triplet therapy reprograms IL21+Th cells. (A) Dot plots showing the ordering of CD4+ T cell clusters by mean expression of HDAC core. Color for z-scaled mean expression; size for percentage of cells in which HDAC core is detected. (B) Box plots showing HDAC core expression levels by IL21+ Th clusters in the DP on-treatment samples. IL21+CXCL13+ Th cells and IL21+IRF4+ Th in UPN30 and UPN51 exhibited higher HDAC scores than UPN50. (C) Volcano plots showing differentially expressed genes between pretreatment and on-treatment samples in IL21+ Th cells from CDP-treated patients. Red dots for significantly higher expression in the on-treatment samples; blue dots for significantly lower expression in the on-treatment samples. Representative genes are highlighted. (D) GSEA plots for 2 pathways with significantly decreased expression in IL21+ Th cells from the on-treatment samples treated by CDP. (E) Bar plots showing the regulon specificity scores of the top 10 transcription factors of IL21+ Th cells. (F) Box plots showing the activities of STAT1 regulon across CD4+ T cell clusters. (G) Genes in IL6/IL21 signaling pathways. Solid lines indicate inferred regulation by STAT1, dashed lines indicate no direct regulation relationship inferred. The differential expression analysis result comparing IL21+ Th cells between on-treatment and pretreatment samples treated by CDP is also shown. Color for log fold change; size for significance. The genes with significant expression difference are highlighted with orange borders. (H) Box plots showing the average expression levels of HDAC core genes in CD30− and CD30+ HRS-like cells. Two-sided Wilcoxon test is applied. (I) Stacked bar plots illustrating relative communication probabilities of ligands and receptors in pretreatment and on-treatment tumors from CDP-treated patients. Interactions from CD8+ T/NK cells to CD30− HRS-like cells with remarkable difference between treatment time points and high communication probabilities in any 1 time point are shown. (J) Network plots showing cell-cell communication probabilities in on-treatment tumors from CDP-treated patients. Dot for cluster, line width for strength of interaction between FASL on CD8+ T/NK cells and FAS on CD30− HRS-like cells. Note, FASL-FAS interactions from CD8+ T/NK cells to CD30− HRS-like in pretreatment tumors were not detected. FASL, FAS ligand; GSEA, Gene Set Enrichment Analysis.

CDP triplet therapy reprograms IL21+Th cells. (A) Dot plots showing the ordering of CD4+ T cell clusters by mean expression of HDAC core. Color for z-scaled mean expression; size for percentage of cells in which HDAC core is detected. (B) Box plots showing HDAC core expression levels by IL21+ Th clusters in the DP on-treatment samples. IL21+CXCL13+ Th cells and IL21+IRF4+ Th in UPN30 and UPN51 exhibited higher HDAC scores than UPN50. (C) Volcano plots showing differentially expressed genes between pretreatment and on-treatment samples in IL21+ Th cells from CDP-treated patients. Red dots for significantly higher expression in the on-treatment samples; blue dots for significantly lower expression in the on-treatment samples. Representative genes are highlighted. (D) GSEA plots for 2 pathways with significantly decreased expression in IL21+ Th cells from the on-treatment samples treated by CDP. (E) Bar plots showing the regulon specificity scores of the top 10 transcription factors of IL21+ Th cells. (F) Box plots showing the activities of STAT1 regulon across CD4+ T cell clusters. (G) Genes in IL6/IL21 signaling pathways. Solid lines indicate inferred regulation by STAT1, dashed lines indicate no direct regulation relationship inferred. The differential expression analysis result comparing IL21+ Th cells between on-treatment and pretreatment samples treated by CDP is also shown. Color for log fold change; size for significance. The genes with significant expression difference are highlighted with orange borders. (H) Box plots showing the average expression levels of HDAC core genes in CD30− and CD30+ HRS-like cells. Two-sided Wilcoxon test is applied. (I) Stacked bar plots illustrating relative communication probabilities of ligands and receptors in pretreatment and on-treatment tumors from CDP-treated patients. Interactions from CD8+ T/NK cells to CD30− HRS-like cells with remarkable difference between treatment time points and high communication probabilities in any 1 time point are shown. (J) Network plots showing cell-cell communication probabilities in on-treatment tumors from CDP-treated patients. Dot for cluster, line width for strength of interaction between FASL on CD8+ T/NK cells and FAS on CD30− HRS-like cells. Note, FASL-FAS interactions from CD8+ T/NK cells to CD30− HRS-like in pretreatment tumors were not detected. FASL, FAS ligand; GSEA, Gene Set Enrichment Analysis.

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