Suppressive regulatory T cells and latent transforming growth factor-ß-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis.

BACKGROUND: Endometriosis is a known cause of infertility. Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-ß (TGF-ß) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-ß is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis. METHODS: PB and PF were collected from 28 women with laparoscopically and histopathologically diagnosed endometriosis and 20 disease-free women who were subjected to laparoscopic surgery. Three subpopulations of CD4+ T lymphocytes (CD45RA+FoxP3low resting Tregs, CD45RA-FoxP3high effector Tregs, and CD45RA-FoxP3low non-Tregs) and CD11b+ mononuclear cells expressing LAP were analyzed by flow cytometry using specific monoclonal antibodies. RESULTS: Proportions of suppressive Tregs (resting and effector Tregs) were significantly higher in the PF samples of patients with endometriosis than in those of control women (P = 0.02 and P < 0.01, respectively) but did not differ between the PB samples of patients and controls. The percentage of CD11b+LAP+ macrophages was significantly lower in PF samples of patients with endometriosis than in those of controls (P < 0.01) but was not altered in the PB samples. CONCLUSION: Proportions of suppressive Tregs and LAP+ macrophages are altered locally in the PF of endometriosis patients.

ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers.

BACKGROUND: Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancer (EAOC). Despite the high rates of recurrence and mortality of EAOC, no prognostic biomarkers have been determined. ADP-ribosylation factor-like protein 4C (ARL4C) has been reported to be involved in various tumor progression processes, but its clinical significance for predicting prognosis in EAOC cases has never been studied. OBJECTIVE: The present study aimed to determine the clinical significance of ARL4C expression in EAOC prognosis. METHODS: ARL4C expression was semi-quantitatively evaluated via immunohistochemistry in 61 EAOC patients, and the correlations between ARL4C expression and clinicopathological data and survival were statistically analyzed. RESULTS: Thirty-six (59%) cases had high levels of ARL4C, which was related to worse 5-year overall survival (OS) (log-rank test, p= 0.036). In multivariate Cox proportional hazard model, high ARL4C expression was a significantly independent predictive factor for worse 5-year OS (hazard ratio = 12.048, p= 0.0201) and 5-year PFS (hazard ratio = 8.130, p= 0.0036). CONCLUSIONS: ARL4C is a biomarker for worse prognosis and a novel therapeutic target in EAOC.