Ferroptosis in T cells: mechanisms, biology and translational opportunities.

Ferroptosis is an iron-dependent form of regulated cell death driven by disrupted iron homeostasis and uncontrolled lipid peroxidation. Various metabolites and enzymes regulate cellular sensitivity to ferroptosis by affecting iron, lipid and redox metabolism. These pathways not only signal ferroptotic cell death but also affect the biology of T cells. The pathways include mechanisms by which iron metabolism regulates T cell activation via transferrin receptor 1-mTOR signalling, mechanisms by which lipid peroxidation drives vulnerability to ferroptosis in tumour-infiltrating CD8+ T cells, and mechanisms by which redox networks are balanced to maintain T cell survival. Here, we highlight the T cell subset-specific effects of ferroptosis-related pathways and ferroptosis susceptibility, and the implications for immunotherapy. We also discuss the emerging therapeutic strategies, including ferroptosis-resistant adoptive T cell therapy and ferroptosis-inducing approaches, that enhance the efficacy of immune checkpoint blockade for cancer treatment. Finally, we propose a framework for precision T cell-based immunotherapies, positioning ferroptosis as a tunable node linking T cell biology to clinical innovations.