A Systems Level Understanding of Iron in the Immune Microenvironment

Eukaryotic cells require iron for biochemical activities and metabolic processes; however, it is a redox active element and can be highly toxic to cells. To evade this toxicity, iron homeostasis in vertebrates is tightly regulated at two levels: organismal and cellular. Dysregulation of iron can have adverse effects and lead to a wide range of diseases. Anaemia of chronic inflammation, for example, is an iron disorder associated with inflammatory disorders, chronic infections, and malignancy, to name a few. Iron stores are not depleted in these disorders, but iron is sequestered in macrophages and dietary iron absorption is also inhibited. Iron overload, on the other hand, causes iron depositions in many vital organs, and excess iron in the brain has been linked to several neurodegenerative disorders. Some studies also suggest that excess iron contributes to cancer development because proteins involved in intracellular iron regulation are differentially expressed, and these cells require more iron. Cancer cells have higher fitness, which results from their interactions with other cells and factors in their microenvironment. Immune cells in the microenvironment can either limit cancer growth or facilitate its spread. It has been proposed that neoplastic cells and the immune system compete for iron. This parallels another completion. Although biological evidence exists to support iron competition, theoretical, computational and experimental work in this area is limited.

Computational models of iron metabolism at both the intracellular and systemic levels have been published, but there has not been enough focus on modeling iron regulation in immune cells and iron trafficking in the tumor microenvironment. This research topic also welcomes experimental approaches of systems biology of iron in cancer, covering both basic research and translational applications. This Research Topic welcomes manuscripts that outline the key molecules and regulatory pathways involved in iron homeostasis in cancer, including iron transporters, storage proteins, and regulatory networks, and describe how these components are integrated to maintain cellular iron balance. Additionally, this Topic welcomes manuscripts that discuss the role of iron in cancer cell proliferation, metastasis, and treatment resistance.

The goal of this topic is to bring together researchers from the mathematical biology, computational biology, and experimental biology communities to advance system-level understanding of irons role in the cancer microenvironment and host-pathogen interactions.

This research topic seeks manuscripts (Original research, methods, reviews and opinion articles) addressing but not limited to:
- Intracellular models of iron handling in immune cells
- Iron handling in tumor microenvironment and its trafficking among immune cells and other cells in the environment.
- Computational models investigating iron regulation in cancer cells
- Experimental validation of computational models demonstrating the role of iron in cancer and the tumour microenvironment

Keywords: iron, iron metabolism, immune, microevironment

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.