Fig. 6: Effects of targeting S1PRs in vitro and vivo.

A Alterations in D18-sphingolipid metabolites in HaCaT, HPV-KI, 2-DG-treated HPV-KI and FSG67-treated HPV-KI cells. The average abundances of every sphingolipid in HaCaT are normalized to 1, and the fold changes of metabolites in HPV-KI, 2-DG- treated HPV-KI, and FSG67- treated HPV-KI are calculated. The Y-axis represents the log₂ FC of each D18 sphingolipid metabolite. Statistical significance is determined using a one-way ANOVA-test (*P < 0.05, **P < 0.01, and ***P < 0.001, ****P < 0.0001, “ns” represents “not significant”). B Assessment of SpHK1/2 activity in HaCaT, HPV-KI, 2-DG-treated HPV-KI and FSG67-treated HPV-KI is shown. C Heatmap illustrating the differential expression of genes involved in the IL-17 pathway between W146-treated HPV-KI and control HPV-KI. D Heatmap depicting the differential expression of genes involved in the IL-17 pathway between JTE013-treated and untreated HPV-KI cells. E S100A8/A9 protein expression in HPV-KI, W146-treated HPV-KI and JTE013-treated HPV-KI cells. F IHC analysis of S100A8/A9 expression in primary tumors from CAT079. G Representative image showing PDX tumors from the PBS-treated group and the W146-treated group. H The histological characteristics of PBS- and W146-treated PDX tumors. H-score of S100A8/A9 and percentage of Ki-67 positive cells in W146-treated PDX/control are calculated. I Image of PDX tumors from DMSO/TWEEN-20/PEG and JTE013- treated group. J Evaluation of histological features in PDX tumors following treatment with PBS or JTE013. H-score of S100A8/A9 and percentage of Ki-67 positive cells in JTE013- treated PDX/control are shown.