Immunomodulatory effects of biodegradable Mg–Cu–Zn alloy in esophageal cancer

Biodegradable magnesium and its alloys have demonstrated ability of anti-tumor cells. However, it remains unclear whether they can regulate the tumor's immune-suppressive microenvironment required for effective treatment of tumor-associated esophageal stenosis. In this study, we investigate the effects of pure Mg, Mg–Cu, and Mg–Cu–Zn alloys on tumor growth and regulation of the tumor immune microenvironment. Our in vitro results show that all three materials effectively suppress the proliferation of human esophageal cancer cells (Eca109 and KYSE30) and mouse AKR esophageal cancer cells. These anti-tumor effects are further validated in vivo using subcutaneous allograft models in immunocompetent mice and xenograft models in immunodeficient mice, where each material inhibits tumor growth and promotes tumor necrosis. Despite these shared anti-tumor effects, only the Mg–Cu–Zn alloy significantly reduces the infiltration of CD163 + M2 tumor-associated macrophages within tumor tissues, indicating a distinct immunomodulatory function. RNA sequencing analysis reveals that the tumor suppression is associated with inhibition of proteasome activity and oxidative phosphorylation, whereas the improved immune microenvironment is linked to enhanced Fc gamma receptor (FcγR)-mediated phagocytosis—an effect not observed with pure Mg or Mg–Cu alloys. These findings demonstrate that the Mg–Cu–Zn alloy not only has anti-tumor properties but also plays a role in regulating the immune microenvironment, making it a promising candidate for biodegradable esophageal stents in tumor-associated stenosis.