Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein

Bibliographic Data

ID23229288
AuthorsWilliam Robert Ochieng (corresponding author), Pingyan Cheng (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Cesar A Corzo (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Noreen Luetteke (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Bin Yu (0000-0001-6980-7345, 1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Srinivas Nagaraj (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Marylin M Bui (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Myrna Ortiz (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612), Wolfgang Nacken (3Institute for Molecular Virology, Center for Molecular Biology of Inflammation, D-48149 Münster, Germany), Clemens Sorg (2Institute of Immunology, University of Münster, D-48149 Münster, Germany), Thomas Vogl (0000-0003-0474-4261, 2Institute of Immunology, University of Münster, D-48149 Münster, Germany), Johannes Roth (2Institute of Immunology, University of Münster, D-48149 Münster, Germany), Dmitry I Gabrilovich (1H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612)
Year2008
Volume205
Issue10
Pages2235-2249
Publication date2008-09-29
Peer ReviewedYes
Open AccessNo
TypeARTICLE
VenueThe Journal of Experimental Medicine (JOURNAL)
Journal identifiersISSN: 0022-1007 • E-ISSN: 1540-9538
PublisherRockefeller University Press (PUBLISHER • US)
DOI10.1084/jem.20080132
PMID18809714
PMCIDPMC2556797
OpenAlexW18809714
LanguageEN
Citations received11
References cited55

Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.

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