Iron and Immunity in Cancer: From Molecular Mechanisms to Clinical Applications

Abstract

Iron is essential for numerous biological functions, including oxygen transport, energy production, and immune defense. In cancer patients, however, iron deficiency and iron overload can adversely affect disease progression and treatment outcomes. Iron deficiency impairs immune responses and can reduce the effectiveness of immunotherapies such as immune checkpoint inhibitors (ICIs). Conversely, excess iron promotes tumor growth, oxidative stress, and immune evasion, creating a microenvironment that reduces treatment efficacy. This review highlights the dual role of iron metabolism in cancer, examining how altered iron levels affect immune cell function, tumor progression, and therapeutic responsiveness. Emerging preclinical and clinical data suggest that personalized iron modulation may improve outcomes through supplementation in deficient patients or iron-reducing strategies in cases of overload. Moreover, combining iron-targeted approaches with immunotherapy could enhance anti-tumor efficacy by synergistically restoring immune competence and targeting tumor vulnerabilities. These findings support the integration of iron assessment and individualized management into routine oncology practice. Further clinical studies are needed to optimize iron-based interventions and to explore their synergy with existing cancer therapies, particularly immunotherapy.