The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis

Immunology. 2011 Jun;133(2):221-38. doi: 10.1111/j.1365-2567.2011.03429.x. Epub 2011 Apr 1.


Myeloid-derived suppressor cells (MDSC) are important to the tumour microenvironment as they actively suppress the immune system and promote tumour progression and metastasis. These cells block T-cell activation in the tumour microenvironment, preventing anti-tumour immune activity. The ability of a treatment to alter the suppressive function of these cells and promote an immune response is essential to enhancing overall therapeutic efficacy. Interleukin-12 (IL-12) has the potential not only to promote anti-tumour immune responses but also to block the activity of cells capable of immune suppression. This paper identifies a novel role for IL-12 as a modulator of MDSC activity, with implications for IL-12 as a therapeutic agent. Treatment with IL-12 was found to alter the suppressive function of MDSC by fundamentally altering the cells. Interleukin-12-treated MDSC exhibited up-regulation of surface markers indicative of mature cells as well as decreases in nitric oxide synthase and interferon-γ mRNA both in vitro and in vivo. Treatment with IL-12 was also found to have significant therapeutic benefit by decreasing the percentage of MDSC in the tumour microenvironment and increasing the percentage of active CD8(+) T cells. Treatment with IL-12 resulted in an increase in overall survival accompanied by a reduction in metastasis. The findings in this paper identify IL-12 as a modulator of immune suppression with significant potential as a therapeutic agent for metastatic breast cancer.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / metabolism
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / pharmacology*
  • Interleukin-12 Receptor beta 1 Subunit / metabolism
  • Interleukin-12 Receptor beta 2 Subunit / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects*
  • Myeloid Cells / metabolism
  • Neoplasm Metastasis*
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • T-Lymphocytes / immunology


  • Biomarkers, Tumor
  • Interleukin-12 Receptor beta 1 Subunit
  • Interleukin-12 Receptor beta 2 Subunit
  • Interleukin-12
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Arg1 protein, mouse
  • Arginase