title: The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis.
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.
authors: Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA.
authors: Catherine E
authors: CE
authors: Steding
authors: Sung-tse
authors: ST
authors: Wu
authors: Yanping
authors: Y
authors: Zhang
authors: Meei-Huey
authors: MH
authors: Jeng
authors: Bennett D
authors: BD
authors: Elzey
authors: Chinghai
authors: C
authors: Kao
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000378:metabolism; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D053711:Interleukin-12 Receptor beta 1 Subunit; D053712:Interleukin-12 Receptor beta 2 Subunit; D018664:Interleukin-12; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase