The imbalance of Th17/Treg in patients with uterine cervical cancer

Zhang, Yan; Ma, Daoxin; Zhang, Yong; Tian, Yongju; Wang, Xuping; Qiao, Yong; Cui, Baoxia

doi:10.1016/j.cca.2011.01.015

Cited by 71 publications

(66 citation statements)

References 37 publications

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“…In the present study, the Treg/Th17 ratio was significantly decreased in patients with DTC, and the positive correlation between Th17 and Treg cells observed in healthy Controls disappeared in patients with DTC. Similar results have been demonstrated in patients with cervical cancer and prostate cancer (21,26). The present study hypothesized that Th17 and Treg cell levels increased owing to immune reactions in the tumor microenvironment.…”

supporting

confidence: 88%

“…Th17 and Tc17 cells have obtained an increasing amount of attention owing to their roles in tumorigenesis; their levels, as well as IL-17 production, are upregulated in the peripheral blood of patients with cancer (19,26,27). Similarly, results from the present study revealed significant increases in the number of Th17 and Tc17 cells in the peripheral blood of patients with DTC.…”

supporting

confidence: 73%

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Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17 cells of patients with differentiated thyroid carcinoma

Zhang

Chen

et al. 2017

Exp Ther Med

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Abstract. T helper 17 (Th17), T cytotoxic 17 (Tc17) and regulatory T (Treg) cells serve important roles in a number of inflammatory and autoimmune diseases. The aim of the present study was to examine the distribution of Th17, Tc17 and Treg cells in patients with differentiated thyroid cancer (DTC) prior to as well as 7, 30 and 90 days following radioactive iodine-131 ( 131 I) therapy, and to elucidate the probable effects of 131 I therapy on Th17/Tc17 and Treg/Th17 cells in patients with DTC. A total of 40 patients with DTC (26 female; 14 male) between the ages of 24 and 72 years, as well as 13 age-and sex-matched healthy subjects were included in this study. The number of Th17, Tc17 and Treg cells in the peripheral blood of patients with DTC and of healthy Controls were assessed by flow cytometry. Th17 and Tc17 cells were counted as percentages of the number of CD3 + T cells; Treg cells were counted as a percentage of the number of CD4 +

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supporting

confidence: 88%

supporting

confidence: 73%

Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17 cells of patients with differentiated thyroid carcinoma

Zhang

Chen

et al. 2017

Exp Ther Med

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“…6 Greater numbers of IL-17-producing cells have also been found both in peripheral blood and in tumor tissues from cancer patients at advanced stages. 7 Although these data suggest that T-helper 17 (Th17) cells potentially have an impact on tumors, the nature and role of Th17 cells in the progression of cervical cancer remain unknown. The presence of HLA-G in CIN patients has been correlated with a worse prognosis and less chance of survival, but the cervical expression of HLA-G and IL-17 has not been evaluated.…”

Section: Impaired Local Cell Immunity Contributes Towards the Pathogementioning

confidence: 99%

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

et al. 2014

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CONTEXT AND OBJECTIVE: Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. DESIGN AND SETTING: Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. RESULTS: There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. CONCLUSION: These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions. RESUMO CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro-quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário. MÉTODOS: Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas. RESULTADOS...

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“…Recently, Th17 cells, a novel T-cell subset with potent proinflammatory and protumorigenic properties (14)(15)(16)(17), were detected in biopsies of patients with high-grade intraepithelial lesions as well as in their peripheral blood (18,19). Notably, the number of infiltrating Th17 cells further increases with progression to invasive cervical cancer (18).…”

Section: Introductionmentioning

confidence: 99%

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression

et al. 2015

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Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4 þ /IL17 þ cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancerbinding protein b (C/EBPb) pathway as shown with a dominantnegative version of C/EBPb and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPb-dependent manner. Th17 cells may in turn maintain chronic inflammation within highgrade cervical lesions to further promote cancer progression.Cancer Res; 75(24); 5248-59. Ó2015 AACR.

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The imbalance of Th17/Treg in patients with uterine cervical cancer

Cited by 71 publications

References 37 publications

Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17 cells of patients with differentiated thyroid carcinoma

Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17 cells of patients with differentiated thyroid carcinoma

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression

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