Correlation of Immune Cells and Cytokines in the Tumor Microenvironment with Elevated Neutrophil-To-Lymphocyte Ratio in Blood: An Analysis of Muscle-Invasive Bladder Cancer

Cancer Invest. 2018;36(7):395-405. doi: 10.1080/07357907.2018.1506800. Epub 2018 Sep 10.

Abstract

We investigated the relationship between Neutrophil-to-lymphocyte ratio (NLR) and the quantities of neutrophil elastase, CD3, Foxp3, and CD204 in tumor-infiltrating cells and circulating cytokines (IL-2, -6, -8, 17a, and TGF-β) in muscle-invasive bladder cancer. IL-6 and IL-8 levels showed a significant correlation with NLR in blood and Foxp3+ cells around the tumor. After co-culture of peripheral blood cells with bladder cancer cell lines, the induction of regulatory T cell (Treg) was higher in T24 whose IL-6 and IL-8 levels were higher. High NLR correlates with increased IL-6 and IL-8 and Treg expression.

Keywords: Foxp3; IL-6; IL-8; NLR; muscle-invasive bladder cancer.

MeSH terms

  • Aged
  • CD4 Lymphocyte Count
  • Cell Line, Tumor
  • Coculture Techniques
  • Cytokines / blood
  • Cytokines / immunology*
  • Cytokines / urine
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Forkhead Transcription Factors / blood
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Muscle, Smooth / immunology*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Neoplasm Invasiveness
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Phenotype
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Microenvironment*
  • Urinary Bladder Neoplasms / blood
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors