Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.

Iron-driven ferroptosis is linked to CAR-T cell dysfunction in multiple myeloma and acute lymphoblastic leukemia, with a diminution phase marked by ferroptosis features and elevated serum iron.

• Why it matters: Durable CAR-T persistence is essential, but the mechanisms behind CAR-T dysfunction are unclear, especially how systemic iron changes relate to loss of function after infusion.
• What they did: Integrated analyses of clinical samples tracked CAR-T expansion and diminution, and preclinical female mouse models plus ex vivo cultures tested whether excess intracellular iron impairs CAR-T function.
• The result: Excess iron promoted ferroptosis via mitochondrial ROS and lipid peroxidation, involving ACSL4-associated lipid remodeling; genetic ACSL4 ablation in CAR-T cells substantially enhanced antitumor efficacy.

AI summary of the abstract · may contain errors · not medical advice · read the paper.