Fig. 2
From: Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins
Lipid chaperone FABP7 protects tumors from immunotherapy-mediated ferroptosis via epigenetic reprogramming. A Fabp7 is among the top upregulated genes in PD1-resistant (Res) tumors compared to PD1-sensitive (Sen) tumors treated with PD1 inhibitors. B Gene set enrichment analysis highlights upregulation of pathways related to fatty acid metabolism, oxidative phosphorylation, and heme metabolism in Res tumors. C, E, F Validation of Fabp7 overexpression at the RNA and protein levels in Res compared to Sen tumors treated with PD1 inhibitors, shown through quantitative PCR and immunohistochemistry (IHC). D Pparg activation assay in Sen, Res, Res-ctrl and Res-shFabp7 cells. G Analysis of acetylation patterns of H3K27ac and H3K9ac in Res versus Sen cells, and in Res-ctrl versus Res-shFabp7 cells, performed via chromatin immunoprecipitation (ChIP) assays coupled with sequencing (ChIP-seq). H H3K9ac and H3K27ac preferentially occur in promoter regions of Sen versus Res cells (70.80% vs 49.75%) and in Res-ctrl versus Res-shFabp7 cells (51.10% vs 33.40%). I Changes in acetylation levels of ferroptosis-related genes, particularly Lpcat3 and Bmal1, with Fabp7 knockdown leading to increased acetylation of Lpcat3 and decreased acetylation of Bmal1. J Integrative Genomics Viewer showing differences in signal enrichment in the promoter region of Lpcat3 for H3K27ac and H3K9ac in Sen versus Res and Res-ctrl versus Res-shFabp7 cells. K Motif enrichment analysis identifying transcription factors regulated by Fabp7, with Pparg binding motifs significantly enriched. L, M Validation of ChIP-seq results by global gene expression profiling in Sen versus Res tumor models, confirming downregulation of Lpcat3 and upregulation of Bmal1 (Arntl) in Res tumors. N Differential expression of Lpcat3 and Bmal1 validated in Sen versus Res tumors, and in Res-ctrl versus Res-shFabp7 tumors treated with either IgG control or PD1 inhibitor using qPCR