Ferroptosis and immunity: rewiring the tumor microenvironment for therapy

Ferroptosis, a distinct form of programmed cell death driven by iron-dependent lipid peroxidation, has emerged as a critical player in cancer biology, influencing both tumor progression and therapeutic responses. This review explores the multifaceted role of ferroptosis within the tumor microenvironment (TME), focusing on its dual potential to promote anti-tumor immunity and immune evasion. Key molecular mechanisms regulating ferroptosis, including the roles of GPX4, SLC7A11, and ACSL4, are examined alongside their interplay with immune cells such as CD8+ T cells, dendritic cells, and macrophages. The review addresses the immunosuppressive effects of ferroptosis-induced signals such as prostaglandin E2 and damage-associated molecular patterns that foster tumor growth. Furthermore, therapeutic strategies leveraging ferroptosis to overcome resistance in cancer treatment, including its integration with immunotherapy and radiotherapy, are discussed. This study underscores the potential of targeting ferroptosis to enhance cancer therapy while emphasizing the need for further research to optimize its application in immunotherapy.