Fig. 5: SK1 targeting enhances ICI efficacy in various cancer models. | Nature Communications

Fig. 5: SK1 targeting enhances ICI efficacy in various cancer models.

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

Fig. 5

a SK1 enzymatic activity in 4T1-Luc cells stably transfected with a control shRNA (shCtrl;) or a SK1-targeted shRNA (shSK1(1)). Data are means ± SEM of three independent experiments. b Cell proliferation. Results are means ± SEM of four independent experiments. c shCtrl and shSK1(1) 4T1-Luc cells were injected in mammary fat pad of BALB/C mice. Mice were then treated with isotype control antibody (iso) or α-CTLA-4. Metastasis index at day 31 in lung of mice injected with shCtrl (upper panel; full columns) or shSK1(1) (lower panel; empty columns) 4T1-Luc tumors and treated (right panel; red columns) or not (left panel; black and white columns) with α-CTLA-4. Inserts: numbers indicate percentage of metastasis-free mice. Data are representative of two independent experiments. d–f Mice were challenged with untransfected Yumm cells and then treated or not with vehicle (Ctrl; black circles with black full line, n = 11 mice), SKI-I (white circles with black dotted line, n = 12 mice), anti-CTLA-4 (red and white triangles; full symbols with full line (without SKI-I n = 12 mice) or empty symbols with dotted line (with SKI-I n = 12 mice). Data are representative of two independent experiments. d Tumor volumes are presented as means ± SEM. e Kaplan–Meier survival curves with log-rank test. f CD8/CD4 + Foxp3 + T-cell ratio in tumors at day 11 (n = 4). g Mice were challenged with untransfected Yumm cells and then treated or not with vehicle (Ctrl; black squares with black line), SKI-I (empty green circles or triangles with green lines) and anti-PD-1 (full blue (without SKI-I) or empty green (with SKI-I) triangles) (n = 12 mice/group). h Mice were inoculated with MC38 and then treated or not with vehicle (Ctrl; black squares with black line), SKI-I (empty green circles or triangles with green lines) and anti-PD-1 (full blue (without SKI-I) or empty green (with SKI-I) triangles) (n = 5 mice /group). Data are representative of two independent experiments. Tumor volumes are presented as means ± SEM. Samples were compared using Mann–Whitney test (a) Kruskal–Wallis test with Dunn’s correction (b, c, and f) or using two ANOVA test (d, g, and h).

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