Figure 5.
PD1-dependent molecular subgroups in CTCL differ in the extent of T-cell exhaustion phenotypes. (A) Proliferative activity of control naive (n = 3) control memory (n = 3) and fully exhausted (n = 4), moderately exhausted (n = 6), and PD1-low (n = 5) CTCL samples. Data represent mean ± standard error of the mean; 1-way analysis of variance (ANOVA), Tukey’s multiple-comparisons test. (B-C) Effector cytokine production assessed by RNA-seq after 6 hours of stimulation with anti-CD3/CD28 beads. P values determined via 1-way ANOVA, Tukey’s multiple-comparisons test. (D) Marker expression of indicated T-cell exhaustion proteins analyzed by CyTOF. P-values calculated by comparing 2-way ANOVA followed by Dunnett’s multiple-comparisons test comparing the control CD4+ group with the indicated CTCL subgroup. (E) Heat map depicting expression determined by RNA-seq of T-cell exhaustion (Tex)–related genes. Color bar (right) indicates z score for each gene. (F) Heat map of FOXM1 gene signatures in CTCL cohorts determined by RNAseq. The ChEA34P value indicates enrichment of these genes for FOXM1-binding sites. (G) Phenotypic features in each indicated subgroup. sig., signature. For all applicable panels, *P < .05, **P < .01, ***P < .001, ****P < .0001, respectively. ChEA, chromatin immunoprecipitation enrichment analysis.

PD1-dependent molecular subgroups in CTCL differ in the extent of T-cell exhaustion phenotypes. (A) Proliferative activity of control naive (n = 3) control memory (n = 3) and fully exhausted (n = 4), moderately exhausted (n = 6), and PD1-low (n = 5) CTCL samples. Data represent mean ± standard error of the mean; 1-way analysis of variance (ANOVA), Tukey’s multiple-comparisons test. (B-C) Effector cytokine production assessed by RNA-seq after 6 hours of stimulation with anti-CD3/CD28 beads. P values determined via 1-way ANOVA, Tukey’s multiple-comparisons test. (D) Marker expression of indicated T-cell exhaustion proteins analyzed by CyTOF. P-values calculated by comparing 2-way ANOVA followed by Dunnett’s multiple-comparisons test comparing the control CD4+ group with the indicated CTCL subgroup. (E) Heat map depicting expression determined by RNA-seq of T-cell exhaustion (Tex)–related genes. Color bar (right) indicates z score for each gene. (F) Heat map of FOXM1 gene signatures in CTCL cohorts determined by RNAseq. The ChEA34 P value indicates enrichment of these genes for FOXM1-binding sites. (G) Phenotypic features in each indicated subgroup. sig., signature. For all applicable panels, *P < .05, **P < .01, ***P < .001, ****P < .0001, respectively. ChEA, chromatin immunoprecipitation enrichment analysis.

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