Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells

Br J Cancer. 2015 Mar 17;112(6):1067-75. doi: 10.1038/bjc.2015.29.


Background: Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape.

Methods: Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines.

Results: EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors.

Conclusions: EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Apoptosis / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Coculture Techniques / methods
  • Cytokines / immunology
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / immunology*
  • Hep G2 Cells
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Inflammation / immunology*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lymphocytes / immunology
  • MCF-7 Cells
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / pathology
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology


  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase