Functional Inversion of Tumor-Associated Macrophages into Iron-Releasing Oxidative Amplifiers: The CD163–HO-1 Bottleneck Hypothesis as a Mechanistic Core of the Sugar–Iron Bomb Model

Key Points

• This project investigates how tumor-associated macrophages can switch roles under iron stress, contributing to disease mechanisms.
• Theoretical model development based on the CD163–HO-1 bottleneck hypothesis.
• Linking macrophage phenotype to iron dysregulation and genomic instability.
• Implementation of predictions within the tumor microenvironment framework.
• Proposed functional inversion of macrophages leads to iron dysregulation and enhanced oxidative stress in tumors.
• Multiple testable predictions generated to support the CD163–HO-1 hypothesis.
• Evidence indicating that this mechanism influences tumor genomic stability.