In this issue of Cancer Cell, Liao et al. demonstrate that CD8(+) T cell-secreted interferon-gamma (IFN-gamma) rewires cancer cell lipid metabolism via the enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4). ACSL4 activates polyunsaturated fatty acids and sensitizes cancer cells to ferroptosis in immunotherapy-relevant settings. These findings provide insights into how the metabolic and immune milieu could be used to promote ferroptosis.
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