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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5457-5466. Prepublished online as a Blood First Edition Paper on March 28, 2008; DOI 10.1182/blood-2008-01-136895. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-01-136895v1 111/12/5457    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sawanobori, Y. Articles by Matsushima, K. Search for Related Content PubMed PubMed Citation Articles by Sawanobori, Y. Articles by Matsushima, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 31, 2008 Accepted March 8, 2008 Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice Yasushi Sawanobori, Satoshi Ueha, Makoto Kurachi, Takeshi Shimaoka, James E. Talmadge, Jun Abe, Yusuke Shono, Masahiro Kitabatake, Kazuhiro Kakimi, Naofumi Mukaida, and Kouji Matsushima* Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States Departent of Immunotherapeutics (Medinet), Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan Divisions of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan * Corresponding author; email: koujim{at}m.u-tokyo.ac.jp. Tumor growth is associated with aberrant myelopoiesis, including the accumulation of CD11b+Gr-1+ myeloid derived suppressor cells (MDSCs) that have the potential to promote tumor growth. However, the identity, growth and migration of tumor-associated MDSCs remain undefined. We demonstrate herein that MDSCs at tumor site were primarily composed of bone marrow- (BM-) derived CD11b+Gr-1hiLy-6Cint neutrophils and CD11b+Gr-1int/dullLy-6Chi macrophages. Unexpectedly, in vivo BrdU labeling and parabiosis experiments revealed that tumor-infiltrating macrophages were replenished more rapidly than neutrophils. CCR2 deficiency caused striking conversion of infiltrating cellular dominance from macrophages to neutrophils in the tumor with the excessive production of CXCR2 ligands and granulocyte-colony stimulating factor (G-CSF) in the tumor without affecting tumor growth. Overall, our data established the identity and dynamics of MDSCs in a tumor-bearing host mediated by chemokines, as well as elucidated unexpected effects of the paucity of macrophages on tumor development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Toda, Y. Terashima, T. Sato, K. Hirose, S. Kanegasaki, and K. Matsushima FROUNT Is a Common Regulator of CCR2 and CCR5 Signaling to Control Directional Migration J. Immunol., November 15, 2009; 183(10): 6387 - 6394. [Abstract] [Full Text] [PDF] G. Solinas, G. Germano, A. Mantovani, and P. Allavena Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation J. Leukoc. Biol., November 1, 2009; 86(5): 1065 - 1073. [Abstract] [Full Text] [PDF] F. Marttila-Ichihara, K. Auvinen, K. Elima, S. Jalkanen, and M. Salmi Vascular Adhesion Protein-1 Enhances Tumor Growth by Supporting Recruitment of Gr-1+CD11b+ Myeloid Cells into Tumors Cancer Res., October 1, 2009; 69(19): 7875 - 7883. [Abstract] [Full Text] [PDF] T. Baba, Y. Nakamoto, and N. Mukaida Crucial Contribution of Thymic Sirp{alpha}+ Conventional Dendritic Cells to Central Tolerance against Blood-Borne Antigens in a CCR2-Dependent Manner J. Immunol., September 1, 2009; 183(5): 3053 - 3063. [Abstract] [Full Text] [PDF] F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability Carcinogenesis, July 1, 2009; 30(7): 1073 - 1081. [Abstract] [Full Text] [PDF] S. Ostrand-Rosenberg and P. Sinha Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer J. Immunol., April 15, 2009; 182(8): 4499 - 4506. [Abstract] [Full Text] [PDF] H.-J. Ko, J.-M. Lee, Y.-J. Kim, Y.-S. Kim, K.-A Lee, and C.-Y. Kang Immunosuppressive Myeloid-Derived Suppressor Cells Can Be Converted into Immunogenic APCs with the Help of Activated NKT Cells: An Alternative Cell-Based Antitumor Vaccine J. Immunol., February 15, 2009; 182(4): 1818 - 1828. [Abstract] [Full Text] [PDF] J.-I. Youn, S. Nagaraj, M. Collazo, and D. I. Gabrilovich Subsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice J. Immunol., October 15, 2008; 181(8): 5791 - 5802. [Abstract] [Full Text] [PDF]

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