PDF(Pubmed)
Abstract：
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 Peptostreptococcus species in gynecological cancer via indoleacrylic acid (IAA). IAA production from Peptostreptococcus 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 Treg and Teff cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, Peptostreptococcus 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 Peptostreptococcus species transplantation, and the intratumoral injection of a conditioned medium from Peptostreptococcus 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 Treg proportion and decreased the M1/M2 ratio. Clinically, P. anaerobius 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 Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.
摘要：
微生物菌群失调对致癌作用的影响日益受到重视，宫颈阴道微生物组在微环境炎症中起着关键作用。这里,我们通过吲哚丙烯酸（IAA）调查了女性生殖道肽链球菌在妇科癌症中的参与。检查了肽链球菌的IAA生产以及细菌培养对体内肿瘤生长的影响。IAA对子宫内膜癌（EC）细胞系中细胞因子产生和吲哚胺-2,3-双加氧酶1（IDO1）表达的影响，以及它们对Treg和Teff细胞的影响，在EC患者和肿瘤移植小鼠中检查M1和M2巨噬细胞群。临床上,肽链球菌种类丰富，IAA,和IDO1表达在EC患者中得到证实。结果表明，肽链球菌在BALB/c裸鼠子宫内诱导IAA产生。肿瘤内注射来自消化链球菌培养物的条件培养基促进了肿瘤移植小鼠的肿瘤生长。IAA上调IL-10表达；IL-10增加IFN-γ表达。IFN-γ在EC细胞系中诱导IDO1表达。表达IDO1的EC细胞与外周血单核细胞的共培养上调了Treg比例并降低了M1/M2比例。临床上,厌氧菌在EC患者的子宫微生物群中比对照更丰富。IAA,在EC组织中IDO1和犬尿氨酸/色氨酸比率均较高，M1/M2比值较低。我们的研究阐明了IDO1诱导与子宫肽链球菌菌群失调之间的联系，并为肽链球菌在I型子宫内膜癌免疫耐受诱导中的作用提供了潜在的理论基础。
