Fig. 4: SK1 inhibition enhances the efficacy of anti-CTLA-4 or anti-PD-1 therapy. | Nature Communications

Fig. 4: SK1 inhibition enhances the efficacy of anti-CTLA-4 or anti-PD-1 therapy.

From: Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1

Fig. 4

Control shRNA (shCtrl) or SK1-targeted shRNA (shSK1(1)) Yumm cells were injected on day 0, and then mice were treated with isotype (iso) control antibody (black lines; shCtrl n = 10 mice, shSK1(1) n = 11 mice), anti-CTLA-4 (red lines; shCtrl n = 11 mice, shSK1(1) n = 11 mice), or anti-PD-1 (blue lines; shCtrl n = 11 mice, shSK1(1) n = 12 mice). a Individual growth curves are depicted for each tumor. Inserts: numbers indicate percentage (%) of tumor-free mice at day 26. b Kaplan–Meier survival curves with log-rank test (iso, circles and black lines; anti-CTLA-4, triangles and red lines; anti-PD-1, squares and blue lines. Full and empty symbols correspond to shCtrl and shSK1(1), respectively). The arrow indicates a second orthotopic injection of shSK1 cells. c Percentages of CD4 + Foxp3 + among CD4 T cells (left panel) or total cells (middle panel) and CD8/CD4 + Foxp3 + T-cell ratio (right panel) at day 11 (iso, black/white boxes; anti-CTLA-4, red boxes; anti-PD-1, blue boxes. Full and empty symbols correspond to shCtrl and shSK1(1), respectively) (n = 9 mice/group). d CCL17 and CCL22 mRNA expression in tumors. Results are representative of two independent experiments (n = 5 mice/group). c, d Samples were compared using Kruskal–Wallis test with Dunn’s correction.

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