PLX223203

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

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Therapeutic 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: Daniele Mercatelli (danielemercatelli@gmail.com) - Giorgi Lab University of Bologna