Elevated Expression of Programmed Death-1 and Programmed Death Ligand-1 Negatively Regulates Immune Response against Cervical Cancer Cells

Zhifang Chen,Donghui Cai,Rong Du,Lingling Fan,Yan Ding,Nannan Pang,Yuejie Zhu,Jianbing Ding

doi:10.1155/2016/6891482

Abstract

The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-β and IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level. PD-1 expression in peripheral blood of cervical cancer patients was related with tumor differentiation, lymph node metastasis, and invasiveness. PD-1/PD-L1 pathway inhibited lymphocyte proliferation but enhanced the secretion of IL-10 and TGF-β in vitro. In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-β, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer. Therefore, PD-1/PD-L1 pathway may become an immunotherapy target in the future.

Highlights

Cervical cancer has the second highest morbidity and mortality rates among all female genital tract malignant tumors [1]
These results suggest that different T cell subsets in patients with cervical cancer have high expression of programmed death-1 (PD-1), and dendritic cell (DC) have high expression of Programmed death ligand-1 (PD-L1)
Correlation analyses between CD4+CD25+PD-1+Treg and transforming growth factor- (TGF-)β, IFN-γ or IL-10 showed that CD4+CD25+PD-1+Treg was positively correlated with TGF-β and IL-10 (r = 0.222 and 0.323, resp.) and was negatively correlated with IFN-γ (r = −0.421) (Figure 3). These results indicate that high expression of PD-1 on Treg cells in cervical cancer patients facilitates the production of TGF-β and IL-10 but inhibits the production of IFN-γ

Summary

Introduction

Cervical cancer has the second highest morbidity and mortality rates among all female genital tract malignant tumors [1]. Programmed death-l (PD-1) is a recently discovered costimulatory molecule on the surface of T cells that binds with PD-ligand to conduct inhibitory second signals. Programmed death ligand-1 (PD-L1) is a member of costimulatory signal B7 family and plays an important role in tumor immune responses [5]. PD-L1 interacts with PD-1 on the surface of T cells, inhibits the activation of tumor antigenspecific T cells, and induces immune tolerance of T cells to tumor cells. This might be one of the important mechanisms by which tumor cells evade immune surveillance [5,6,7]. We detect PD-1 and PD-L1, as well as related cytokines in cervical lesion development process, and analyze

Methods

Results

Conclusion