Macrophage ferroptosis in hematologic malignancies: emerging mechanisms and therapeutic implications

Ferroptosis, a distinct form of regulated cell death, has attracted significant attention due to its critical role at the intersection of cellular metabolism, redox biology, and various human diseases. Macrophages play a key role in maintaining systemic iron balance, and their specific polarization states influence the regulation of ferroptotic processes. However, the therapeutic potential of ferroptosis in cancer is frequently limited by tumor-associated macrophages (TAMs), representing a significant challenge in applying immunotherapy to hematologic malignancies. Notably, inducing ferroptosis in macrophages themselves also holds therapeutic promise. This review synthesizes recent advances in macrophage ferroptosis research to clarify its role in disease pathogenesis. Importantly, we highlight the translational potential of the ferroptosis-TAM axis, suggesting that biomarker-guided modulation of this pathway, via novel nanocarriers or combination treatments, represents a paradigm-shifting strategy to overcome drug resistance and restore antitumor immunity in hematologic malignancies.