| Literature DB >> 24810636 |
José Medina-Echeverz1, Lydia A Haile, Fei Zhao, Jaba Gamrekelashvili, Chi Ma, Jean-Yves Métais, Cynthia E Dunbar, Veena Kapoor, Michael P Manns, Firouzeh Korangy, Tim F Greten.
Abstract
Myeloid derived suppressor cells (MDSCs) play a critical role in suppression of immune responses in cancer and inflammation. Here, we describe how regulation of Bcl2a1 by cytokines controls the suppressor function of CD11b(+) Gr-1(high) granulocytic MDSCs. Coculture of CD11b(+) Gr-1(high) granulocytic MDSCs with antigen-stimulated T cells and simultaneous blockade of IFN-γ by the use of anti-IFN-γ blocking antibody, IFN-γ(-/-) effector T cells, IFN-γR(-/-) MDSCs or STAT1(-/-) MDSCs led to upregulation of Bcl2a1 in CD11b(+) Gr-1(high) cells, improved survival, and enhanced their suppressor function. Molecular studies revealed that GM-CSF released by antigen-stimulated CD8(+) T cells induced Bcl2a1 upregulation, which was repressed in the presence of IFN-γ by a direct interaction of phosphorylated STAT-1 with the Bcl2a1 promotor. Bcl2a1 overexpressing granulocytic MDSCs demonstrated prolonged survival and enhanced suppressor function in vitro. Our data suggest that IFN-γ/ STAT1-dependent regulation of Bcl2a1 regulates survival and thereby suppressor function of granulocytic MDSCs.Entities:
Keywords: Bcl2a1; G-MDSC; GM-CSF; IFN-γ; Immunotherapy; Vaccine
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Year: 2014 PMID： 24810636 PMCID： PMC4140991 DOI： 10.1002/eji.201444497
Source DB: PubMed Journal: Eur J Immunol ISSN： 0014-2980 Impact factor: 5.532