Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 6, 2020; 8(1): 11-19
Published online Jan 6, 2020. doi: 10.12998/wjcc.v8.i1.11
Oncogenic role of Tc17 cells in cervical cancer development
Zun-Sheng Zhang, Ying Gu, Bing-Gang Liu, Hong Tang, Yu Hua, Jun Wang
Zun-Sheng Zhang, Ying Gu, Bing-Gang Liu, Hong Tang, Yu Hua, Jun Wang, Department of Obstetrics and Gynecology, Shanghai Seventh People’s Hospital, Shanghai 200120, China
Author contributions: Zhang ZS and Gu Y designed the research; Tang H and Hua Y performed the research; Liu BG analyzed the data; Wang J wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Shanghai Seventh People’s Hospital Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jun Wang, MSc, Attending Doctor, Department of Obstetrics and Gynecology, Shanghai Seventh People’s Hospital, No. 358, Datong Road, Gaoqiao Town, Pudong New Area, Shanghai 200120, China. wanchuang3069629@163.com
Received: October 7, 2019
Peer-review started: October 7, 2019
First decision: November 13, 2019
Revised: November 18, 2019
Accepted: November 30, 2019
Article in press: November 30, 2019
Published online: January 6, 2020
Processing time: 91 Days and 8.6 Hours
Abstract
BACKGROUND

As one of the subsets of CD8+ T cells, Tc17 cells have recently been identified and are characterized by the secretion of interleukin (IL)-17, which is related to inflammatory diseases.

AIM

To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.

METHODS

Flow cytometry assay, immunohistochemistry, and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer. Prior to cell suspension culture, ELISA was carried out to measure the production of IL-6, IL-1β, IL-23, CXCL12, and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer. In addition, multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.

RESULTS

Compared with normal tissues, Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients. Cancer cells produced a greater amount of IL-6, IL-1β, and IL-23, which in turn promoted Tc17 cell polarization. Unlike the traditional cytotoxic CD8+ T cells, Tc17 cells secreted IL-17, which subsequently promoted CXCL12 expression in tumor cells, eventually enhancing the proliferation and migration of tumor cells. Thus, the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.

CONCLUSION

Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer. We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.

Keywords: Cervical cancer; Tc17 cells; Interleukin-17; Cancer development; Biological function; Oncogenic role

Core tip: Inflammation contributes to cancer development. In this study, it was found that cervical cancer-elicited inflammation increased Tc17-polarizing cytokine production, which attenuated cytotoxic CD8+ T cell development. The high level of interleukin-17 production by Tc17 cells led to CXCL12 upregulation and cancer cell migration. Consistent with the oncogenic role of Tc17 cells in cancer development, the ratio of cancer-infiltrating Tc17 cells was highly associated with poor prognosis in patients with cervical cancer. Thus, our data demonstrate that Tc17 cells can be induced in cervical cancers and serve as a meaningful index in the prognosis of patients with cervical cancer.