Cuproptosis-immunity crosstalk informs strategy to overcome immunotherapy resistance

A reciprocal circuit between cuproptosis (copper-induced cell death) and antitumor immunity was identified in which CD8⁺ T cell-derived IFN-γ increases tumor cell susceptibility to cuproptosis. Combining engagement of this cuproptosis axis with PD-L1 checkpoint blockade amplified tumor cell killing and overcame immunotherapy resistance in preclinical models. The findings, published in Cell, reveal a previously unrecognized mechanistic link that could inform new combination strategies for immunotherapy-refractory cancers.