The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer

Abstract

BackgroundRecently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC).MethodsFlow cytometry was used to determine the expression of interferon gamma (IFN-γ), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-α and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-α were examined.ResultsTh22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-α and IL-6 was significantly high in CC patients.ConclusionsOur results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.

T- and NK-cell populations with regulatory phenotype and markers of apoptosis in circulating lymphocytes of patients with CIN3 or microcarcinoma of the cervix: evidence for potential mechanisms of immune suppression

“…Several researchers have documented elevated frequency of circulating CD4 lymphocytes expressing Treg markers in blood samples of women with persistent HPV, CIN or CC [ 14 – 16 ]. Other studies have also identified that patients with CIN1/2 and CIN3 display altered numbers of some rare populations of circulating lymphocytes, which exert immunoregulatory/proinflammatory functions, such as Tc17 [ 17 ], Th17 and Th22 [ 18 ], NK-like CD8 cells [ 19 ], and CD4 + NKG2D + cells [ 20 ]. Deregulated expression of several activation markers and co-stimulatory/inhibitory molecules (such as NKG2D, CD28, and PD-1) was also described in peripheral blood lymphocytes from women with invasive cervical carcinoma or preinvasive lesions [ 21 – 23 ].…”

“…Deregulated expression of several activation markers and co-stimulatory/inhibitory molecules (such as NKG2D, CD28, and PD-1) was also described in peripheral blood lymphocytes from women with invasive cervical carcinoma or preinvasive lesions [ 21 – 23 ]. Additionally to immunoregulatory cell populations, some important changes in the levels of related cytokines (for example, IL-4, −6, −8, −10, −17, −22, −23, TNFα, IFNγ and other) have been revealed in the serum of CIN/CC patients [ 16 , 18 , 19 ], with TGFβ supposed to be one of the key factors operating the mechanisms by which regulatory lymphocytes are induced and can exert their suppressive effect [ 16 , 23 ].…”

Treatment to sustain a Th17‐type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

“…Several studies have shown correlations between cancer presence and increased levels of Th17 cells or Th17 cell‐associated cytokines, raising suggestions that the Th17 cells contribute to the tumor development and progression. This includes increased levels of Th17 cells or IL‐17 in patients with cervical cancer, hypopharyngeal carcinoma, gastric cancer and lung cancer . The contribution of Th17 cells to inflammation, such as in the gut, has been implicated in the development of colon cancer .…”

“…This includes increased levels of Th17 cells or IL-17 in patients with cervical cancer, hypopharyngeal carcinoma, gastric cancer and lung cancer. [14][15][16][17] The contribution of Th17 cells to inflammation, such as in the gut, has been implicated in the development of colon cancer. 18 In addition to studies showing associations between the presence of Th17 cells and cancer, a few interventional studies have been conducted, although results of some of these studies are conflicting.…”

Interleukin-22 derived from cervical cancer-associated fibroblasts accelerates senescence of normal fibroblasts and promotes expression of tumorigenesis-related factors in HeLa cells

“…IL-22, the main cytokine released by Th22 cells, belongs to the IL-10 cytokine family [12]. Th22 cell population and IL-22 concentration were significantly elevated in the peripheral blood of cervical cancer patients compared to that of healthy controls [13]. These findings suggested that IL-22 may be involved in the pathogenesis of cervical cancer.…”