Myeloid-derived suppressor cells (MDSCs) expansion is a hallmark of cancer. Three major MDSC subsets defined as monocytic (M)-MDSCs, polymorphonuclear (PMN)-MDSCs and early stage (e)MDSCs can be revealed in human diseases. However, the clinical relevance and immunosupressive pattern of these cells in epithelial ovarian cancer (EOC) are unknown. Therefore, we performed a comprehensive analysis of each MDSC subset and immunosupressive factors in the peripheral blood (PB), peritoneal fluid (PF), and the tumor tissue (TT) samples from EOC and integrated this data with the patients' clinicopathological characteristic. MDSCs were analyzed using multicolor flow cytometry. Immunosuppressive factors analysis was performed with ELISA and qRT-PCR. The level of M-MDSCs in the PB/PF/TT of EOC was significantly higher than in healthy donors (HD); frequency of PMN-MDSCs was significantly greater in the TT than in the PB/PF and HD; while the level of eMDSCs was greater in the PB compared with the PF and HD. Elevated abundance of tumor-infiltrating M-MDSCs was associated with advanced stage and high grade of EOC. An analysis of immunosuppressive pattern showed significantly increased blood-circulating ARG/IDO/IL-10-expressing M- and PMN-MDSCs in the EOC patients compared with HD and differences in the accumulation of these subsets in the three tumor immune microenvironments (TIME). This accumulation was positively correlated with levels of TGF-β and ARG1 in the plasma and PF. Low level of blood-circulating and tumor-infiltrating M-MDSCs, but neither PMN-MDSCs nor eMDSCs was strongly associated with prolonged survival in ovarian cancer patients. Our results highlight M-MDSCs as the subset with potential the highest clinical significance.

These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7-H4+ macrophages that enable the restriction of this same activation as labor progresses.

The study was undertaken to evaluate macrophage-derived chemokine (CCL22) levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n = 93) in relation to regulatory T cells (Tregs; n = 75). The peritoneal fluid CCL22 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients than in patients with benign tumors-serous cystadenoma (n = 32). There was no difference in plasma levels of CCL22 in EOC patients compared with the non-cancer and healthy volunteers (n = 10). There were no significant differences in the plasma and PF CCL22 levels based on tumor grade. However, women with stage IV FIGO (International Federation of Gynecologists and Obstetricians) had significantly higher plasma CCL22 levels than patients with stages I and III. Women with stage I FIGO had significantly higher PF CCL22 levels than patients with stages II and III. Women with endometrioid cystadenocarcinoma had higher PF CCL22 levels than women with undifferentiated carcinoma. The percentage of tumor-infiltrating Tregs (11.06 %) was significantly higher compared to PF (3.05 %) and peripheral blood (PB) (2.01 %). Moreover, the percentage of Tregs was higher in the PF than in the PB of EOC patients. There were no significant differences in the PB, PF, and tumor-infiltrating Tregs percentage based on tumor stage, grade, or histology. Elevated levels of CCL22 found in the ascites could create a chemokine gradient aiding in Treg cells migration. Increased Tregs percentage in the local microenvironment of ovarian cancer might be an important mechanism of immunosuppression.

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Introduction and objective. Data on the possible role of peritoneal fluid free radical-mediated oxidative damage in the pathogenesis of endometriosis still remains inconsistent. The aim of the study was to determine iron metabolism markers and their influence on oxidative stress parameters in the peritoneal fluid of women with endometriosis. Materials and method. 110 women with endometriosis and 119 patients with benign ovarian cysts were included in the study. All visible peritoneal fluid was aspirated during laparoscopy from the anterior and posterior cul-de-sacs. under direct vision to avoid blood contamination. Haemoglobin, iron, total oxidative status, and total antioxidant status were measured using standard colourimetric kits. Results. Haemoglobin, iron levels, as well as total oxidative status values were significantly higher, whereas total antioxidant status values were significantly lower in the peritoneal fluid of patients with endometriosis, in comparison to the reference groups. No differences were observed in peritoneal fluid concentrations of all parameters measured in relation to the phase of the menstrual cycle. Conclusions. Peritoneal fluid of women with endometriosis is characterized by disrupted iron metabolism. This is most likely related to an increased number of erythrocytes in the peritoneal cavity of endometriotic women, which leads to a higher concentration of haemoglobin in this environment. Impaired iron homeostasis may have a significant influence on the pathophysiology of peritoneal endometriosis by the direct impact of haemoglobin derivatives and/or formation of the pro-inflammatory and pro-oxidative environment. Peritoneal cavity oxidative stress occurs predominantly in women in advanced stages of the disease.