IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2

Sci Rep. 2013 Dec 9;3:3456. doi: 10.1038/srep03456.

Abstract

The proinflammatory cytokine Interleukin 17A (hereafter named IL-17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(-) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(-) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biopsy
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Docetaxel
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • MAP Kinase Signaling System* / drug effects
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Receptors, Estrogen / metabolism
  • Taxoids / pharmacology

Substances

  • Antineoplastic Agents
  • Interleukin-17
  • Receptors, Estrogen
  • Taxoids
  • Docetaxel
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3