Copper metabolism: A novel strategy for tumor immunotherapy resistance

Copper is an essential nutrient for organisms, and alterations in copper metabolism often indicate a diseased state. Recently, the role of copper metabolism in tumor immunotherapy has garnered increasing attention. Cuproptosis, along with the restoration of dysregulated copper homeostasis, can modulate PD-L1 expression, evoke antitumor immune responses, enhance the infiltration of immune cells into tumors, and reprogram the tumor microenvironment. Therefore, targeting copper metabolism presents a novel strategy to overcome resistance to tumor immunotherapy. In this review, we summarize the fundamental aspects of copper metabolism, the mechanisms underlying cuproptosis and copper homeostasis, the impacts of copper metabolism on the immune system, and the applications of copper-based compounds (including copper chelators, copper ionophores, and copper complex-based agents) and nanoparticles (NPs) in cancer immunotherapy.