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

Mediators Inflamm. 2016:2016:6891482. doi: 10.1155/2016/6891482. Epub 2016 Sep 5.

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.

MeSH terms

  • Adult
  • B7-H1 Antigen / blood*
  • B7-H1 Antigen / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / blood*
  • Programmed Cell Death 1 Receptor / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Uterine Cervical Dysplasia / blood
  • Uterine Cervical Neoplasms / blood*
  • Uterine Cervical Neoplasms / genetics

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Programmed Cell Death 1 Receptor
  • Transforming Growth Factor beta
  • Interleukin-10