Extended Data Figure 10. Pharmacological depletion of glycosphingolipids impacts immune evasion.

a. Abundance of ceramide-derived lipid species in HY15549 cells left untreated (gray) or treated with 10 µM eliglustat for 24 hours. Signal is normalized to cholesterol levels of each sample. Mean ± SEM, n = 3 biological replicates.

b. Abundance of hexosyl-1-ceramide species in HY15549 cells left untreated (gray) or treated with 10 µM eliglustat for 24 hours. Signal is normalized to cholesterol levels of each sample. Mean ± SEM, n = 3 biological replicates.

c. Abundance of hexosyl-2-ceramide species in HY15549 cells left untreated (gray) or treated with 10 µM eliglustat for 24 hours. Signal is normalized to cholesterol levels of each sample. Mean ± SEM, n = 3 biological replicates.

d. Proliferation of wildtype HY15549 (left) or KP LUAD (right) cells left untreated (gray) or pretreated with eliglustat for 24 hrs (pink) and the indicated concentrations of interferon-γ (IFNγ) for 96 hrs. Mean ± SD; n = 3 biological replicates.

e. Weights (left) and image (right) of wildtype KP LUAD tumors grown in C57BL/6J mice on the indicated treatment regimens. Mean ± SEM; n = 6 (HY15549 −/−, +/−, −/+, KPLUAD −/+) or 7 (others) mice/ group; scale bar = 1 cm. Data were analyzed using a one-way ANOVA with Tukey’s multiple test correction.

f. Survival analysis of TCGA PDAC patients with high (blue) or low (pink) expression of SPTLC1, SPTLC2, and KDSR. N = 177. Error bands = 95% confidence interval.