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

Catherine E. Steding, Sung tse Wu, Yanping Zhang, Meei Huey Jeng, Bennett D. Elzey, Chinghai Kao

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)221-238
Number of pages18
JournalImmunology
Volume133
Issue number2
DOIs
StatePublished - Jun 1 2011

Keywords

  • Gr-1/CD11b
  • IL-12
  • Immune suppressor
  • Macrophage
  • MDSC

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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