GSE155031 Transcriptome analysis of SH-SY5Y neuroblastoma cells treated with copper and copper chelators (Dextran-Catechin - DC, and Tetraethylenepentamine pentahydrochloride - TEPA) in the presence or absence of interferon gamma

Contributors : Florida Voli ; Emanuele Valli ; Luigi Lerra ; Kathleen Kimpton ; Federica Saletta ; Federico M Giorgi ; Daniele Mercatelli ; Jourdin R Rouaen ; Sylvie Shen ; Jayne E Murray ; Aria Ahmed-Cox ; Giuseppe Cirillo ; Chelsea Mayoh ; Paul A Beavis ; Michelle Haber ; Joseph A Trapani ; Maria Kavallaris ; Orazio VittorioSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTherapeutic checkpoint antibodies blocking PD1/PD-L1 signaling have radically improved clinical outcomes in cancer. However, the regulation of PD-L1 expression on tumor cells is still poorly understood. Here we show that intra-tumoral copper levels influence PD-L1 expression in cancer cells. Copper supplementation enhanced PD-L1 expression at mRNA and protein levels in cancer cells and RNAseq revealed that copper regulates key signaling pathways mediating PD-L1-driven cancer immune evasion. Conversely, copper chelators inhibited phosphorylation of STAT3 and EGFR and promoted ubiquitin-mediated degradation of PD-L1.. Overall, this study reveals an important role for copper in regulating PD-L1 and suggests that anti-cancer immunotherapy might be enhanced by pharmacologically reducing intra-tumor copper levels.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research