PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome

Sci Rep. 2021 Mar 18;11(1):6400. doi: 10.1038/s41598-021-85966-0.

Abstract

The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • Biomarkers, Tumor / genetics
  • CD8 Antigens / genetics
  • CD8-Positive T-Lymphocytes
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD8 Antigens
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor