Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

Abstract

New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.

Keywords

• iron metabolism
• ferroptosis
• cancer
• innate immune response
• adaptive immune response tumor microenvironment