Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T helper cells

Immunol Lett. 2013 Jan;149(1-2):123-33. doi: 10.1016/j.imlet.2012.11.002. Epub 2012 Nov 15.

Abstract

Research on T helper 17 (Th17) cells with regard to immunoediting has revealed elusive results. Whereas enhanced Th17 response and related molecules such as interleukin (IL)-17, IL-21, IL-22, IL-23 and STAT3 accompanied tumor induction and progression, finding that tumor growth/stage was negatively correlated with increased infiltration of Th17 cells in the tumor mass has prompted elucidation of various antitumor mechanisms elicited by Th17 and their related molecules. The pro-tumor efficacy of Th17 response included promotion of neutrophilia and induction of angiogenic (e.g. VEGF, MMP2 and MMP9) and anti-apoptotic factors (e.g. Bcl-XL), as well as expansion and activation of myeloid-derived suppressor cells, which facilitate generation of tumor-specific regulatory T cells. Other tumor immunogenic settings revealed anti-tumor pathways including induction of cytotoxic activity, expression of MHC antigens, the ability Th17 cells to reside within the tumor, and to convert into IFN-γ producers. Notably, Th17 cell related molecules exert indirect pro- or anti-tumor effects via inducing viral persistence or mediating protective mechanisms against bacterial and viral infection. Herein, the recent literature revealing such immunoediting events mediated by Th17 cells and their associated molecules as delivered by various experimental regimens and observed in cancer patient are revised, with a focus on some proposed anti-cancer therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / immunology
  • Humans
  • Matrix Metalloproteinase 2 / immunology
  • Matrix Metalloproteinase 9 / immunology
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy
  • STAT3 Transcription Factor / immunology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • Cytokines
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9