Selective disruption of lipid peroxide homeostasis in intratumoral regulatory T cells by targeting FSP1 enhances cancer immunity.

ABSTRACT: A burgeoning approach to treating cancer is the pharmacological induction of ferroptotic cell death of tumor cells. However, the impact of disrupting antiferroptotic pathways in the broader tumor microenvironment (TME), such as in immune cells, is still undefined and may complicate treatments. Here, we show that ferroptosis suppressor protein 1 (FSP1/Aifm2) is critically required for regulatory T cell (T_reg cell) resistance to ferroptosis and their immunosuppressive function within the TME. Compared to other canonical ferroptosis regulators such as GPX4 and NRF2, only FSP1 was induced upon T cell activation. Deletion of Aifm2 in all T cells, or T_reg cells specifically, enhanced tumor control by selectively disrupting T_reg cell immunosuppressio

SUBMITTER: Castillo JG 

PROVIDER: S-EPMC12829571 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature