Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients

Int J Mol Sci. 2021 Oct 26;22(21):11563. doi: 10.3390/ijms222111563.

Abstract

The latest literature demonstrates the predominant role of the programmed cell death axis (PD-1/PD-L1/PD-L2) in ovarian cancer (OC) pathogenesis. However, data concerning this issue is ambiguous. Our research aimed to evaluate the clinical importance of PD-L1/PD-L2 expression in OC environments. We evaluated the role of PD-L1/PD-L2 in OC patients (n = 53). The analysis was performed via flow cytometry on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) and monocytes/macrophages (MO/MA) in peripheral blood, peritoneal fluid (PF), and tumor tissue (TT). The data were correlated with clinicopathological characteristics and prognosis of OC patients. The concentration of soluble PD-L1 (sPD-L1) and PD-1 in the plasma and PF were determined by ELISA. We established an accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the tumor microenvironment. We showed an elevated level of sPD-L1 in the PF of OC patients in comparison to plasma and healthy subjects. sPD-L1 levels in PF showed a positive relationship with Ca125 concentration. Moreover, we established an association between higher sPD-L1 levels in PF and shorter survival of OC patients. An accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the TT and high sPD-L1 levels in PF could represent the hallmark of immune regulation in OC patients.

Keywords: immune suppression; immunotherapy; ovarian cancer; programmed cell death pathway; tumor microenvironment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen-Presenting Cells / metabolism*
  • Antigen-Presenting Cells / pathology*
  • Ascitic Fluid / metabolism
  • Ascitic Fluid / pathology
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*
  • Tumor Microenvironment / physiology
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein