Cuproptosis enters the cancer-immunity circuit.

In this issue of Cell, Lei et al. reveal a reciprocal circuit in which cuproptotic tumor cells promote dendritic cell activation and CD8+ T cell priming, whereas T cell-derived IFN-γ sensitizes tumor cells to FDX1-dependent cuproptosis. This self-reinforcing interaction provides a mechanistic rationale for combining cuproptosis induction with PD-L1 blockade to overcome immunotherapy resistance.