Macrophages and macrophage extracellular vesicles confer cancer ferroptosis resistance via PRDX6-mediated mitophagy inhibition.

ABSTRACT: Ferroptosis has emerged as a promising therapeutic target in cancer therapy, with the tumor microenvironment (TME) playing a pivotal role in regulating ferroptosis. Although macrophages contribute to ferroptosis regulation within TME, the underlying mechanisms remain unclear. In this study, we demonstrate that macrophages consistently attenuate GPX4 inhibitor-induced lipid peroxidation and cell death in various tumor cell lines, whereas their resistance to cysteine transport inhibitor-triggered ferroptosis varies across cell types. This tumor protection from ferroptosis is mediated through macrophage-tumor cell contact and the delivery of macrophage-derived extracellular vesicles (Mφ-EV). Transcriptomic and proteomic analyses revealed that macrophages and Mφ-EV enhance glutathione metaboli

SUBMITTER: Zheng N 

PROVIDER: S-EPMC12391288 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature