Application of Immunoprofiling Using Multiplexed Immunofluorescence Staining Identifies the Prognosis of Patients with High-Grade Serous Ovarian Cancer

Int J Mol Sci. 2021 Sep 6;22(17):9638. doi: 10.3390/ijms22179638.

Abstract

Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420-0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.

Keywords: CD8; FoxP3; PD-L1; immunoprofiling; multiplex IHC; ovarian cancer; quantitative analysis.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis
  • Biomarkers, Tumor / analysis*
  • CD8 Antigens / analysis
  • Cystadenocarcinoma, Serous / diagnosis
  • Cystadenocarcinoma, Serous / metabolism*
  • Female
  • Fluorescent Antibody Technique / methods*
  • Forkhead Transcription Factors / analysis
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / metabolism*
  • Prognosis
  • Staining and Labeling / methods*
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors