For instance, T-DXd preferentially accumulates in HER2-low breast cancer perivascular zones, where HMGB1 release drives DC maturation via TLR4/NF-κB signaling, whereas hypoxic cores exhibit hypoxia-inducible factor 1 alpha (HIF-1α)-mediated M2 macrophage polarization and Treg expansion, creating immunosuppressive barriers [12, 105]. This evidence concerns the gene HIF1A and breast carcinoma.