The Prevalence And Significance Of Th22 And Th17 Cells In The Peripheral Blood Of Cervical Cancer

Background and objective:Cervical cancer (CC) is one of the leading gynecological cancers in developing countries and the main etiology behind is the persistent infection of high-risk HPV. Even though the incidence of HPV is high but with the help of cell mediated immunity they can be cleared spontaneously.A very few cases may develop into advanced CC from precancerous lesion which may indicate a substantial role of immune regulation in controlling of HPV associated lesions and cancer progression. We know that one subgroup of lymphocytes T helper cells (Th) has an essential role in immune system. A newly discovered T cell subset-Th22 cells which are detected in autoimmune diseases have the ability to secret IL-22 and TNF-a. But the nature of Th22 cells are not properly clear in human cancer. Recently some studies concluded that Th22 cells have the contribution in the progression of hepatocellular and gastric carcinoma which recommended that Th22 cells may be involved in the development of tumors. No study was carried out to understand the involvement of these cells in cervical cancer (CC). Our research aimed to explore the possible status of Th22 cells in the pathogenesis and progression of cervical cancer.Methods:By using flow cytometry, the percentage of Th22 cells and Th17 cells in cervical cancer, CIN patients and Healthy controls (HC) were examined. To better understand the regulation of Th22 cells in CIN and cervical cancer,we determined mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC) in peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction. The levels of IL-22 in PB plasma were examined by enzyme-linked immunosorbent assay.Results:The percentages of Th22 cells (all P< 0.01) and Th17 cells (CIN:P< 0.05; CC:P< 0.01) in CIN and CC patients were significantly increased compared with those in controls. The percentage of Th22 cells in cervical cancer was higher than that in CIN patients (P＜0.01). An positive correlation between Th22 cells and Th17 cells was found in CIN patients (r=0.40,P<0.05). Th22 cells showed a positive correlation with Th17 cells in CC patients (r=0.60, P<0.01). The level of IL-22 in plasma was significantly increased in CC patients compared with that in controls (P< 0.05).Notably, in CC patients, the increased Th22 prevalence was associated with lymph node metastases and deep stromal invasion (P<0.05). The mRNA expression of RORC was notebaly increased in CC (P<0.01) and CIN (P<0.05).In addition, CC patients (r=0.624, P<0.01) and CIN patients (r=0.618, P<0.01) had a positive correlation between RORC and Th17 cells. Furthermore, CC patients (r=0.611, P<0.01) and CIN patients (r=0.523, P<0.05) showed a positive correlation between RORC and Th22 cells.Conclusions:Our results indicate that the elevation of circulating Th22 cells, and Th17 cells conjointly contribute to the pathogenesis and progression of CC and potentially be cellular targets for therapeutic intervention.