Cell Death Discov. 2026 May 23. doi: 10.1038/s41420-026-03147-2. Online ahead of print.
ABSTRACT
Ferroptosis, a unique form of regulated cell death driven by iron-dependent lipid peroxidation, and macrophage polarization, which reflects the high plasticity of the immune system, represent two prominent frontiers in contemporary life sciences. Emerging evidence suggests a profound bidirectional interplay between these processes, mediated by iron metabolism reprogramming, lipid signaling molecules, and complex molecular axes such as RAGE-STAT3. This review systematically summarizes the biological mechanisms of ferroptosis and macrophage polarization, delving into their interaction within the tumor microenvironment, inflammatory responses, and cardiovascular and neurodegenerative diseases (e.g., Alzheimer's and Parkinson's). We highlight how M1 macrophages induce ferroptosis through pro-inflammatory cytokines and reactive oxygen species, while M2 macrophages inhibit it by modulating iron homeostasis and antioxidant capacity. Finally, we discuss therapeutic strategies targeting the ferroptosis-macrophage polarization axis, providing a theoretical foundation and novel perspectives for developing precise medical interventions.
PMID:42177194 | DOI:10.1038/s41420-026-03147-2