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The role of interleukin‐12 on modulating myeloid‐derived suppressor cells, increasing overall survival and reducing metastasis
Author(s) -
Steding Catherine E.,
Wu Sungtse,
Zhang Yanping,
Jeng MeeiHuey,
Elzey Bennett D.,
Kao Chinghai
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03429.x
Subject(s) - immune system , myeloid derived suppressor cell , cancer research , tumor microenvironment , metastasis , immunology , cd8 , immunotherapy , interleukin , biology , cytokine , medicine , cancer , suppressor
Summary 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.