Esophageal cancer-derived microvesicles induce regulatory B cells

Cell Biochem Funct. 2015 Jul;33(5):308-13. doi: 10.1002/cbf.3115. Epub 2015 May 25.

Abstract

The role of B cells in the generation of cancer-immune tolerance is unclear. This study aims to investigate the role of cancer-derived microvesicles (Mvcs) in the generation of transforming growth factor (TGF)-β(+) B cells. In this study, esophageal cancer (Eca) cells were isolated from surgically removed cancer tissue. Mvcs were purified from the culture supernatant and characterized by Western blotting. The immune suppression assay was carried out with a cell culture model and flow cytometry. The results showed that Eca-derived Mvcs were LAMP1 positive and carried MMP9. Exposure to the Mvcs induces naive B cells to differentiate into TGF-β-producing regulatory B cells; the latter show immune suppressor functions on CD8(+) T-cell proliferation. In conclusion, Eca-derived Mvc can induce TGF-β(+) B cells; the latter suppress CD8(+) T-cell activities. The MMP9-laden Mvcs may be a new therapeutic target in the treatment of Eca.

Keywords: B lymphocyte; TGF-β; esophagus cancer; extracellular vesicles; immune tolerance; microvesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes, Regulatory / cytology
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Differentiation
  • Cell Proliferation
  • Cell-Derived Microparticles / metabolism*
  • Cells, Cultured
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Humans
  • Matrix Metalloproteinase 9 / metabolism*
  • Peptides / metabolism
  • Protein Precursors / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tumor Escape

Substances

  • Peptides
  • Protein Precursors
  • Transforming Growth Factor beta
  • latency-associated propeptide, TGF-beta
  • MMP9 protein, human
  • Matrix Metalloproteinase 9