Research Papers:

Aberrant frequency of TNFR2+ Treg and related cytokines in patients with CIN and cervical cancer

Teng Zhang, Jun Jiao, Xinlin Jiao, Lu Zhao, Xinli Tian, Qing Zhang, Daoxin Ma and Baoxia Cui _

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Oncotarget. 2018; 9:5073-5083. https://doi.org/10.18632/oncotarget.23581

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Teng Zhang1, Jun Jiao1, Xinlin Jiao1, Lu Zhao1, Xinli Tian2, Qing Zhang1, Daoxin Ma3 and Baoxia Cui1

1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong, PR China

2Department of Obstetrics and Gynecology, Weifang Maternal and Child Health Hospital, Weifang 261011, Shandong, PR China

3Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, Shandong, PR China

Correspondence to:

Baoxia Cui, email: [email protected]

Keywords: cervical cancer; TNFR2; TNFR1; regulatory T cells; cytokines

Received: July 14, 2017     Accepted: December 11, 2017     Published: December 22, 2017


Regulatory T (Treg) cells expressing tumor necrosis factor receptor 2 (TNFR2) are highly suppressive and are associated with immune homeostasis in various diseases. However, the role of TNFR2+Treg subset and relevant cytokines in the development of cervical cancer (CC) remained unclear. In this study, 72 patients with CC, 30 patients with cervical intraepithelial neoplasia (CIN) and 30 healthy volunteers were enrolled. The level of circulating TNFR2+Tregs was investigated through flow cytometry. The plasma concentrations of soluble TNFR1 (s-TNFR1) and soluble TNFR2 (s-TNFR2) were determined by enzyme-linked immunosorbent assay. In addition, the mRNA expression levels of TNF-α, TNFR1, TNFR2, and Foxp3 were measured using real-time polymerase chain reaction. Results showed that both peripheral and tumor infiltrating TNFR2+Tregs significantly increased in patients with CIN and CC and levels of circulating s-TNFR1 and s-TNFR2 increased in patients with CC. Moreover, the percentage of peripheral TNFR2+Tregs was inversely correlated with the clinical stages of CC. Furthermore, the mRNA expression levels of TNF-α, TNFR2, and Foxp3 increased in patients with CIN and CC. Overall, these results indicate that TNFR2+Tregs and relevant cytokines contribute to CC development and are promising targets in future immunotherapeutic approaches.

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