High Serum Levels of Interleukin-18 Are Associated With Worse Outcomes in Patients With Breast Cancer

Anticancer Res. 2019 Sep;39(9):5009-5018. doi: 10.21873/anticanres.13691.

Abstract

Background/aim: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer.

Patients and methods: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated.

Results: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs.

Conclusion: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.

Keywords: Breast cancer; IL18; cancer immunity; cytokine; prognosis.

MeSH terms

  • Biomarkers, Tumor*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cytokines / blood
  • Cytokines / metabolism
  • Female
  • Humans
  • Interleukin-18 / blood*
  • Leukocyte Count
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Reference Values
  • Retrospective Studies
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Cytokines
  • IL18 protein, human
  • Interleukin-18