Abstract
Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis and cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here we investigated the involvement of the female genital tract microbiome in a gynaecological cancer. We transferred Peptostreptococcus species into the uteri of BALB/c nude mice and observed indoleacrylic acid (IAA) production. Intratumoral injection of conditioned medium from bacterial cultures into tumour-xenografted mice for 2 months promoted tumour growth. IAA upregulated IL-10 expression by M2 macrophages, which increased IFN-γ expression by CD8+ T cells. IFN-γ induced indoleamine-2,3-dioxygenase 1 (IDO1) expression in endometrial cancer (EC) cell line. Co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the proportion of regulatory T cells and decreased the M1/M2 ratio. Importantly, P. anaerobius was more abundant amongst the uterine microbiota of clinical EC patient samples than control samples. IAA, IDO1, and the kynurenine/tryptophan ratio were all higher in EC tissue than in healthy tissue, and the M1/M2 ratio was lower. Thus, we conclude that the overabundance of uterine commensal Peptostreptococcus species in EC induces IDO1 expression by producing IAA. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis.
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