목적: TAM (Tumor-associated macrophages) are a significant component of the TME and are known for their dual roles in cancer. They can either inhibit or promote tumor growth, depending on their polarization state. The M1 macrophages generally possess anti-tumor properties, whereas M2 macrophages are associated with tumor promotion and While there have been studies on macrophage polarization and the roles of EPHA3 and CD47 in cancer, the combined effect of targeting these molecules in the context of recurrent head and neck cancer has not been extensively explored. study aims to investigate the effects of EPHA3 monoclonal antibody and anti-CD47 antibody on the polarization of macrophages and their subsequent impact on the phagocytosis of recurrent head and neck cancer cells. 방법:Utilizing various cancer cell lines, we assessed the expression of EPHA3, CD47, and markers for M1 and M2 macrophage subtypes through western blotting, FACS, and FISH in both parent and radioresistant cell lines. The effects of EPHA3 and CD47 treatments were tested in vitro and in vivo on human and mouse cell lines, focusing on tumor growth, phagocytosis, and immune cell infiltration alterations. 결과:Our results indicated that over-expression of EPHA3 and CD47 is associated with decreased phagocytosis in radioresistant cancer cells, particularly in the M2 macrophage subset. However, combined treatment with EPHA3 and CD47 antibodies significantly reduced tumor growth and enhanced phagocytosis both in vitro and in vivo. This was accompanied by an increase in M1 macrophage markers (iNOS, TNF-α, IL-6) and a decrease in M2 markers (arginase 1, CD206, IL-10, P-STAT1), as evidenced by flow cytometry. Additionally, EPHA3 antibody treatment was found to potentiate CD47-mediated repolarization towards the M1 phenotype. 결론:In conclusion, our findings suggest that treatment with EPHA3 and anti-CD47 antibodies promotes tumor cell phagocytosis and inhibits tumor growth by inducing a shift in macrophage phenotype towards the M1 subtype in vivo. This highlights the potential therapeutic value of targeting macrophage polarization in the treatment of recurrent head and neck cancer.