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

This project proposes the CD163–HO-1 bottleneck hypothesis as a molecular mechanism underlying pathological iron dysregulation within the Sugar–Iron Bomb framework. Under sustained hemolytic stress, tumor-associated macrophages may transition from protective hemoglobin scavengers into pathological oxidative amplifiers, a process termed "functional inversion." The model generates multiple testable predictions linking macrophage phenotype, iron dysregulation, and genomic instability within the tumor microenvironment. **Related Publication (Zenodo):** - Primary: https://doi.org/10.5281/zenodo.20068648