The Imbalance Of Th17/Treg In Patients With Uterine Cervical Cancer

Background:Th17/Treg was reported to play critical roles in immunoregulation, and its imbalance may lead to autoimmune diseases and allergic reactions. And IL-21 was the highly expressed cytokine of Th17 cells, which can regulate the differentiation, development and function of Th17 cells through autocrine pathway. Information on Th17/Treg in cancer bearing hosts is still limited.Methods:We examined the expression of IL-17, Foxp3 and IL-21 in uterine cervical cancer (UCC) patients, cervical intraepithelial neoplasia (CIN) patients and healthy controls by flow cytometry. Interleukin (IL)-17-producing CD4+ cells as Th17 cells, CD4+CD25+Foxp3+ T cells as Treg cells and Interleukin (IL)-21-producing CD4+ cells as CD3+CD8-IL-21+ T cells were expressed as a percentage of the total CD4+ cells.Results:Compared with healthy controls, patients with UCC or CIN had a higher proportion of Th17 cells (PUCC=0.0001, PCIN=0.0056) and CD3+CD8-IL-21+ T cells (PUCC=0.035, PCIN=0.041). UCC patients also revealed a significant increase in Treg number (P<0.0001), while CIN patients did not. Notably, in UCC patients, the increased Th17 cells and CD3+CD8-IL-21+ T cells prevalence were associated with clinical stage (PTh17=0.0281, P CD3+CD8-IL-21+ Tcells=0.0160), lymph node metastases (PTh17=0.0015, PCD3+CD8-IL-21+T cells=0.046) and vasoinvasion (PTh17<0.0001, PCD3+CD8-IL-21+ T cells<0.0001), while the elevated CD3+CD8-IL-21+ T cells frequency was also associated with tumor size (P<0.0001), and the increased Treg frequency was associated with tumor differentiation (P=0.009). Furthermore, the frequencies of Th17 cells and CD3+CD8-IL-21+T cells were positively correlated in healthy controls and uterine cervical cancer patients. Remarkably, an attractive imbalance of Th17/Treg was observed in UUC and CIN patients. And in UCC patients with lymph node metastases or vasoinvasion, the ratio of Thl7/Treg was significantly higher than that in negative patients respectively.Conclusions:Our results indicated a possible role of Thl7 cells in UCC patients and CIN patients correlated to Treg cells and CD3+CD8-IL-21+T cells, and the imbalance of Th17/Treg may be involved in the development and progression of UCC.