Uterine Commensal Species Contribute to IDO1 Induction in Endometrial Cancer via Indoleacrylic Acid.

Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis, and the cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here, we investigated the involvement of the female genital tract species in gynecological cancer via indoleacrylic acid (IAA). IAA production from species and the effect of bacterial culture on tumor growth in vivo were examined. The impact of IAA on cytokine production and indoleamine-2,3-dioxygenase 1 (IDO1) expression in an endometrial cancer (EC) cell line, as well as their effect on T and T cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, species abundance, IAA, and IDO1 expression were verified in EC patients. The results showed that IAA production was induced in the uteri of BALB/c nude mice by species transplantation, and the intratumoral injection of a conditioned medium from cultures into tumor-grafted mice promoted tumor growth. IL-10 expression was upregulated by IAA; IFN-γ expression was increased by IL-10. IFN-γ induced IDO1 expression in the EC cell line. The co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the T proportion and decreased the M1/M2 ratio. Clinically, was more abundant amongst the uterine microbiota of EC patients than the control. The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine dysbiosis and provides a potential rationale for the role of species in immune tolerance induction in type I endometrial cancer.