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PMID: 18809714 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Journal of experimental medicine ·Vol. 205 ·No. 10 ·2008-09-29 ·Pages 2235-49

Cheng P, Corzo CA, Luetteke N, Yu B, Nagaraj S, Bui MM, Ortiz M, Nacken W, Sorg C, Vogl T, Roth J, Gabrilovich DI

Abstract

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.

MeSH Terms
Animals Bone Marrow Cells/cytology,physiology Calgranulin B/genetics,metabolism Cell Differentiation/physiology Dendritic Cells/cytology,physiology Embryonic Stem Cells/cytology,physiology Female Hematopoietic Stem Cells/cytology,physiology Macrophages/cytology,physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Cells/cytology,physiology NIH 3T3 Cells Neoplasms/immunology,pathology Phenotype Reactive Oxygen Species/metabolism STAT3 Transcription Factor/genetics,metabolism
Chemicals
Calgranulin B Reactive Oxygen Species STAT3 Transcription Factor
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Cheng Pingyan
H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA.
Corzo Cesar A
Luetteke Noreen
Yu Bin
Nagaraj Srinivas
Bui Marylin M
Ortiz Myrna
Nacken Wolfgang
Sorg Clemens
Vogl Thomas
Roth Johannes
Gabrilovich Dmitry I
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20080132
Published
2008-09-29
Epub
2008-00-22
Pages
2235-49
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2556797
Subset
IM
Grants
NCI NIH HHS · P30-CA76292 · United States
NCI NIH HHS · R01 CA084488 · United States
NCI NIH HHS · P30 CA076292 · United States
NCI NIH HHS · CA100062 · United States
NCI NIH HHS · R01 CA100062 · United States
NCI NIH HHS · CA84488 · United States
External Links
PubMed source DOI: 10.1084/jem.20080132 PMC Full Text View journal details
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