Copper Homeostasis, Emerging Central Players in Cancer Immunotherapy

Copper ions serve as multifunctional signalling molecules that are integral to various cellular processes in vivo, including cell proliferation, apoptosis and migration. The storage, transport and homeostatic regulation of intracellular copper are closely linked to mitochondrial function. These biological processes play a significant role in the occurrence and development of tumours. Furthermore, cuproptosis, a newly identified mode of cell death, has been associated with multiple cellular processes, such as mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. In this study, we investigate the relationship between dysregulation of mitochondrial-centered copper homeostasis in cancer and the activation of the NF-κB signalling pathway, as well as the transcriptional regulation of PD-L1. Our findings reveal a potential connection between copper ion signalling and the activation of anti-tumour immunity. We outline the advantages and challenges of copper-targeted anticancer therapeutic strategies and emphasise the necessity for a deeper understanding of copper homeostasis regulation in cancer. We review the evidence of altered copper homeostasis in tumours, discuss the current understanding of the mechanisms underlying these changes, and consider the potential implications for cancer progression. The imbalance of copper in tumours may present opportunities for the development of novel imaging biomarkers and therapeutic agents.