Extended Data Fig. 6 | Nature Immunology

Extended Data Fig. 6

From: Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1+CD8+ T cells

Extended Data Fig. 6

(A) t-SNE dimension reduction was performed on influenza (FLU)-specific CD8+ T cells cultured with (0 ng/ml, 30 ng/ml, or 80 ng/ml of IL-21) after 7 d of culture. Overlay dot plot (left) and normalized colored-marker expression (right) of indicated cytotoxic, activation and exhaustion-associated genes are visualized on the t-SNE map. (B) Production of IL-2 (adju P = 0.5928, mono P = 0.4921, dual P = 0.0259), TNF (adju P = 0.1299, mono P = 0.1040, dual P = 0.9452), IFN-γ (adju p = 0.4922, mono p = 0.0107, dual p = 0.1160) and CCL-3/4 (adju P = 0.7148, mono P = 0.9785, dual P = 0.6762) was determined by CD4+ T cells after PMA/ ionomycin stimulation. Scattered dot plots indicate frequency of cytokine-positive cells by patient groups (adjuvant (adju) (n = 11), palliative (mono) (n = 14), and combination therapy with anti-CTLA-4 (n = 20)) and time point. (C) IgG (adju P = 0.7145, mono P = 0.3281, dual P = 0.0026), IgA (adju P = 0.2101, mono P = 0.8796, dual P = 0.0064) and IgM (adju P = 0.3031, mono P = 0.9645, dual P = 0.6387) concentration in patient plasma was measured by nephelometry (adjuvant (adju) (n = 14), palliative (mono) (n = 15), and combination therapy with anti-CTLA-4 (n = 15)). Samples pre-therapy are represented in open circles and post-therapy in open squares in scatter plots. Bar and error bar represent median and 95% CI in scatter plots. Statistical significance was determined by two-sided paired Wilcoxon signed-rank test (* P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001).

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