Increased interleukin-35 expression in tumor-infiltrating lymphocytes correlates with poor prognosis in patients with breast cancer

Cytokine. 2017 Jan:89:76-81. doi: 10.1016/j.cyto.2016.09.012. Epub 2016 Sep 24.

Abstract

Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay. IL-35 expression in the tissue specimens was analyzed by immunohistochemistry. It was shown that 39.1%, 43.6% and 17.3% of the 110 patients were absent, weak, and strong IL-35 expression in the TILs, respectively. Strong IL-35 expression in TILs was significantly associated with age >50years, tumor size >2cm, TNM stage III, and negative ER (All P<0.05). Patients with elevated IL-35 expression in TILs had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with weak or no IL-35 expression (All P<0.05). High plasma IL-35 levels were significantly associated with TNM stage III and lymph node metastasis (All P<0.05). Plasma IL-35 level and IL-35 expression in the TILs of breast cancer tissues may be a valuable biomarker in the development and prognosis of IDC.

Keywords: Breast cancer; Interleukin-35; Invasive ductal carcinoma; Tumor-infiltrating lymphocytes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Interleukins / biosynthesis*
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Survival Rate
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Biomarkers, Tumor
  • Interleukins
  • Neoplasm Proteins
  • interleukin-35, human