<scp>SAA1</scp> Induces <scp>TGF</scp> ‐β1 Secretion by Ovarian Cancer Cells, Leading to <scp>M2</scp> Macrophage Polarization and Inhibition of <scp>NK</scp> Cell Activity

Natural killer (NK) cells play an important role in immune surveillance of tumors. The molecular mechanism of NK cells killing ovarian cancer cells remains elusive. This study attempts to show a potential mechanism of NK cell killing by polarization of M2 macrophages. Serum amyloid A1 protein (SAA1) expression in ovarian cancer tissue and its correlation with macrophage markers and TGF-β1 expression were analyzed using bioinformatics. TGF-β1 levels were determined by western blot and ELISA. Immunohistochemistry, flow cytometry, and immunofluorescence were employed to analyze the expression of M1 and M2 macrophage markers and NK cell markers. NK cytotoxicity was assessed using the lactate dehydrogenase assay and ELISA. TUNEL staining was used to detect tumor cell apoptosis. The xenograft tumor mouse model was utilized to reveal the in vivo function of the SAA1/TGF-β1 axis. SAA1 was upregulated in ovarian cancer and positively correlated with M2 macrophage marker expression. Overexpression of SAA1 upregulated M2 macrophage markers in mouse tumor tissue. In vitro experiments showed that SAA1 induced polarization of M2 macrophages, and this effect was reversed by anti-TGF-β1 treatment. SAA1 inhibited the expression of NK cell activity markers and cytotoxicity by mediating M2 macrophage polarization. Finally, we demonstrated in vivo that partial reversal of the effects of SAA1 overexpression on NK cell activity and M2 macrophage polarization was achieved through anti-TGF-β1 therapy. SAA1 repressed NK cell killing in ovarian cancer by facilitating M2 macrophage polarization through TGF-β1. The findings suggested that SAA1 may be a target for ovarian cancer therapy.