Patient inflammatory status and CD4+/CD8+ intraepithelial tumor lymphocyte infiltration are predictors of outcomes in high-grade serous ovarian cancer

Gynecol Oncol. 2018 Oct;151(1):10-17. doi: 10.1016/j.ygyno.2018.07.025. Epub 2018 Aug 2.

Abstract

Background: High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histologic type of ovarian cancer. To date, there are no reliable biomarkers to effectively predict patient prognosis. Studies have demonstrated inflammation and tumor infiltrating lymphocytes (TILs) correlate with a bad and good prognosis, respectively. Here, we sought to evaluate systemic inflammation and TILs as early prognostic markers of survival.

Methods: Neutrophil-to-lymphocyte ratio (NLR) and serum Lactate Dehydrogenase (LDH) were used as indicators of systemic inflammation. NLR, serum LDH, tumor infiltrating lymphocytes (TILs), PDL1 and quality of debulking surgery were evaluated as determinants of progression-free survival (PFS) and overall survival (OS) in a cohort of 128 HGSOC patients.

Results: Initial univariate analysis showed that systemic inflammation measures (NLR and serum LDH), debulking surgery, and intra-epithelial TILs have a significant impact on both PFS and OS. After adjustment for several variables, multivariate analyses confirmed intraepithelial CD4+ T-cells, systemic inflammation measures, PDL1 and debulking surgery as determinants of better OS and PFS.

Conclusions: Systemic inflammation and TILs are early determinants of OS in HGSOC. Other variables such as the quality of debulking surgery and PDL1 also improve survival of patients. Regarding TIL sub-populations, intraepithelial CD4+ cells are associated to an increase in both PFS and OS. We also confirmed previous reports that demonstrate intraepithelial CD8+ cells correlate with an increase on PFS in ovarian cancer. A combined score using systemic inflammation and TILs may be of prognostic value for HGSOC patients.

Keywords: Inflammation; Lactate Dehydrogenase; Neutrophil-to-lymphocyte ratio; Ovarian cancer; Overall survival; Tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cystadenocarcinoma, Serous
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / blood
  • Inflammation / immunology*
  • Inflammation / mortality
  • Inflammation / pathology
  • L-Lactate Dehydrogenase / blood
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Neoplasm Grading
  • Neutrophils / immunology
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovary / pathology
  • Ovary / surgery
  • Prognosis
  • Prospective Studies
  • Retrospective Studies

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • L-Lactate Dehydrogenase