Clinical Significance of Programmed Death Ligand‑1 and Intra-Tumoral CD8+ T Lymphocytes in Ovarian Carcinosarcoma

PLoS One. 2017 Jan 26;12(1):e0170879. doi: 10.1371/journal.pone.0170879. eCollection 2017.

Abstract

Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients' clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS.

MeSH terms

  • Adult
  • Aged
  • Ascitic Fluid / immunology
  • Ascitic Fluid / pathology
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology*
  • Carcinosarcoma / diagnosis*
  • Carcinosarcoma / genetics
  • Carcinosarcoma / mortality
  • Carcinosarcoma / pathology
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / pathology
  • Middle Aged
  • Organ Specificity
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Prospective Studies
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human

Grants and funding

This work was supported by the Science and Technology Commission of Shanghai Municipality (Grant No.12411950300). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.