Journal article
Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion
F Voli, E Valli, L Lerra, K Kimpton, F Saletta, FM Giorgi, D Mercatelli, JRC Rouaen, S Shen, JE Murray, A Ahmed-Cox, G Cirillo, C Mayoh, PA Beavis, M Haber, JA Trapani, M Kavallaris, O Vittorio
Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2020
Abstract
Therapeutic checkpoint antibodies blocking programmed death receptor 1/programmed death ligand 1 (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 intratumoral copper levels influence PD-L1 expression in cancer cells. Deep analysis of the The Cancer Genome Atlas database and tissue microarrays showed strong correlation between the major copper influx transporter copper transporter 1 (CTR-1) and PD-L1 expression across many cancers but not in corresponding normal tissues. Copper supplementation enhanced PD-L1 expression at mRNA and protein levels in cancer cells and RN..
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Awarded by Australian Research Council
Funding Acknowledgements
The authors acknowledge financial support from National Health and Medical Research Council (NHMRC) Career Development Fellowship (APP1164960 to O. Vittorio); Cure Cancer Australia, Priority-driven Collaborative Cancer Research Scheme (APP 1141582 to O. Vittorio); Cancer Institute NSW Career Development Fellowship (RG161875 to O. Vittorio); Tour de Cure Grant; The Ross Trust Foundation; NHMRC Program grant (APP1091261 to M. Kavallaris); NHMRC Principal Research Fellowship (APP1119152 to M. Kavallaris); ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (CE140100036 to M. Kavallaris); NHMRC Program grant (APP1091261 to M. Haber); Cancer Institute New South Wales Program grant (14/TPG/1-13 to M. Haber). The authors also thank the Sydney Children's Tumour Bank Network (A/Prof D. Catchpoole and Ms A. Yuksel from the Children's Hospital at Westmead Tumour Bank) for providing the TMA slides and related clinical information for this study.