Favorable prognostic impact of Natural Killer cells and T cells in high-grade serous ovarian carcinoma

Acta Oncol. 2020 Jun;59(6):652-659. doi: 10.1080/0284186X.2019.1711173. Epub 2020 Jan 14.

Abstract

Introduction: The aim of the present study was to investigate the prognostic impact of intratumoral cytotoxic T cells, Natural Killer (NK) cells, neutrophils and PD-L1 expression in patients with epithelial ovarian cancer.Methods: All patients diagnosed with high-grade serous carcinoma (HGSC) in Denmark in 2005 were included in the study. Immunohistochemical staining for PD-L1, CD8, CD66b and CD57 was performed on tumor tissue from 283 patients. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS).Results: The median OS for HGSC patients was 30 months. It was 45 months in patients with high level of CD57+ NK cells (≥10 cells/mm2) compared with 29 month in patients with low level (<10 cells/mm2) (p = .0310). The median OS was 37 and 25 months in patients with high vs. low level of CD8+ T cells (cutoff 80 cells/mm2) (p = .0008). In multivariate analysis, high numbers of CD57+ NK cells and CD8+ T cells remained independent markers of favorable OS, adjusted hazard ratio (HR) 0.67; p = .041, and HR 0.72; p = .020, respectively. PD-L1 expression was associated with improved OS (37 months vs. 22 months, p = .0006), but was only borderline significant in the multivariate analysis (HR 0.77, p = .061). CD66b + neutrophils had no association with OS.Conclusions: In patients with HGSC tumor-infiltrating CD57+ NK cells and CD8+ T cells had favorable prognostic impact, while PD-L1 expression had borderline favorable prognostic significance. CD66b + neutrophils had no prognostic association. These findings may influence future immunotherapy development.

MeSH terms

  • Aged
  • Antigens, CD / analysis
  • Antigens, CD / metabolism
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / metabolism
  • CD57 Antigens / analysis
  • CD57 Antigens / metabolism
  • CD8 Antigens / analysis
  • CD8 Antigens / metabolism
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / metabolism
  • Cell Count
  • Cystadenocarcinoma, Serous / blood
  • Cystadenocarcinoma, Serous / chemistry
  • Cystadenocarcinoma, Serous / mortality*
  • Cystadenocarcinoma, Serous / pathology
  • Denmark
  • Female
  • GPI-Linked Proteins / analysis
  • GPI-Linked Proteins / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Immunity, Cellular
  • Immunohistochemistry
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / cytology*
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Middle Aged
  • Neoplasm Grading
  • Neutrophils / chemistry
  • Neutrophils / cytology*
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • T-Lymphocytes, Cytotoxic / chemistry
  • T-Lymphocytes, Cytotoxic / cytology*
  • Time Factors

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • CD57 Antigens
  • CD8 Antigens
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins