Involvement of regulatory T cells and Th17 cells in ovarian endometriosis and ovarian epithelial tumors

Endometriosis is a chronic inflammatory disorder defined as abnormal growth of endometrial tissue at ectopic sites, most often on the ovary. Women with endometriosis are at higher risk of developing ovarian cancer. We recently generated a mouse model for ovarian endometriosis, using the previously established LSL‐KrasG12D mice, which we crossed with MUC1 transgenic mice. Following intra‐bursal administration of Cre‐encoding adenovirus, the MUC1Kras mice develop de novo, endometriosis‐like lesions. Interestingly, these mice show an increased percentage of FoxP3+ regulatory T cells in their spleens and para‐aortic lymph nodes but fewer Th17. We also investigated the pattern of FoxP3, IL‐17, TGF‐b, IL‐1 and IL‐6 mRNA expression in human ovarian endometriosis and ovarian cancer using qRT‐PCR. Our results from a total of 23 patients (normal donors, physiological ovarian cysts, endometriosis, ovarian tumors with paired ascites) show that FoxP3 was detected in the ascites of all tested patients and in the majority of tumor specimens but also in 6 out of 9 of patients with endometriosis, confirming our results in mice. IL‐17 was also up‐regulated in 55% of endometriosis cases and it was highly up‐regulated in ovarian cysts. Further studies on the immune imbalance in premalignancy (endometriosis) and ovarian cancer in mice and humans are in progress. Research support from the Continuing Medical Research Fund (AMV).