Tc17 Cells in Patients with Uterine Cervical Cancer

Yan Zhang,Xin Liu,Daoxin Ma,Baoxia Cui,Youzhong Zhang,Fei Hou,Beihua Kong,Jian-Xin Gao

doi:10.1371/journal.pone.0086812

Abstract

BackgroundThe existence of Tc17 cells was recently shown in several types of infectious and autoimmune diseases, but their distribution and functions in uterine cervical cancer (UCC) have not been fully elucidated.MethodsThe frequency of Tc17 cells in peripheral blood samples obtained from UCC patients, cervical intraepithelial neoplasia (CIN) patients and healthy controls was determined by flow cytometry. Besides, the prevalence of Tc17 cells and their relationships to Th17 cells and Foxp3-expressing T cells as well as microvessels in tissue samples of the patients were assessed by immunohistochemistry staining.ResultsCompared to controls, patients with UCC or CIN had a higher proportion of Tc17 cells in both peripheral blood and cervical tissues, but the level of Tc17 cells in UCC tissues was significantly higher than that in CIN tissues. Besides, the increased level of Tc17 in UCC patients was associated with the status of pelvic lymph node metastases and increased microvessel density. Finally, significant correlations of infiltration between Tc17 cells and Th17 cells or Foxp3-expressing T cells were observed in UCC and CIN tissues.ConclusionsThis study indicates that Tc17 cell infiltration in cervical cancers is associated with cancer progression accompanied by increased infiltrations of Th17 cells and regulatory T cells as well as promoted tumor vasculogenesis.

Highlights

Uterine cervical cancer (UCC), the second most prevalent malignancy in women worldwide [1], is considered to be an important immunogenic tumor, as human papillomavirus (HPV) high-risk subtypes cause multistep carcinogenesis from cervical intraepithelial neoplasia (CIN) through carcinoma in situ to invasive cancer and metastatic cancer
The percentage of Tc17 cells was significantly higher in uterine cervical cancer (UCC) patients (0.4960.37%, P = 0.0076) and CIN patients (0.5160.39%, P = 0.0149), compared to that in healthy controls (0.2760.27%) (Fig. 2a)
No significant difference was found between the level of Tc17 cells in CIN and that in UCC patients (P.0.05)

Summary

Introduction

Uterine cervical cancer (UCC), the second most prevalent malignancy in women worldwide [1], is considered to be an important immunogenic tumor, as human papillomavirus (HPV) high-risk subtypes cause multistep carcinogenesis from cervical intraepithelial neoplasia (CIN) through carcinoma in situ to invasive cancer and metastatic cancer. The responses of the host immune systems, especially the cellular immune response, play an important role in the control of both HPV infections and HPV-associated neoplastic formation [2,3]. A recently described Th subset, CD4+ T cells with IL-17 production (Th17 cells), has been shown to play an important role in the conditions of inflammation, autoimmunity and allergic reactions [5,6,7]. The subsets of IL-17+CD8+ T cells (Tc17 cells), recently found in several conditions of infection and autoimmune diseases [9,10,11,12], have not been fully studied and their biological functions are still lacking. The existence of Tc17 cells was recently shown in several types of infectious and autoimmune diseases, but their distribution and functions in uterine cervical cancer (UCC) have not been fully elucidated

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