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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

Abstract

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 composed primarily of bone marrow-derived CD11b+Gr-1hiLy-6Cint neutrophils and CD11b+Gr-1int/dullLy-6Chi macrophages. Unexpectedly, in vivo bromodeoxyuridine (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 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 and elucidated unexpected effects of the paucity of macrophages on tumor development.

  • Submitted January 30, 2008.
  • Accepted March 8, 2008.
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