The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage

Abstract Bachground: Cervical cancer is a common malignant disease in female patients accompanied by active autophagy in tumor cells. However, much remains unknown about the regulatory factors of autophagy and its effect on immune response.Methods: Autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine, and epacadostat was detected by western blot and autophagy detection kit. After co-cultured with pre-treated HeLa and SiHa cells, U937 was detected by flow cytometry to analyze the CD80, CD86, CD163, CD206 expression and the phagocytosis. Results: IFN-γ could significantly increase the autophagy level of HeLa and SiHa cells by promoting the indoleamine-2,3-dioxygenase-1 (IDO1) expression. HeLa and SiHa cells treated with recombinant human IFN-γ could significantly increase the phagocytosis and CD80, CD86 expression of U937, and this effect was associated with the autophagy in tumor cells. IFN-γ treatment and IDO1 overexpression promote tryptophan depletion and kynurenine accumulation in cervical cancer cells, and the latter was proved to be more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophage. In vivo, IDO1 overexpression could significantly restrict the tumor growth in C57 mice, and the phagocytosis of macrophage was enhanced.Conclusions: IFN-γ promotes the autophagy of cervical cancer cell possibly through IDO1 expression and kynurenine metabolism, and further promotes macrophage phagocytosis in cervical cancer.