Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice.
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-1(hi)Ly-6C(int) neutrophils and CD11b(+)Gr-1(int/dull)Ly-6C(hi) 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.
Sawanobori
Yasushi
Y
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ueha
Satoshi
S
Kurachi
Makoto
M
Shimaoka
Takeshi
T
Talmadge
James E
JE
Abe
Jun
J
Shono
Yusuke
Y
Kitabatake
Masahiro
M
Kakimi
Kazuhiro
K
Mukaida
Naofumi
N
Matsushima
Kouji
K
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D016130:Immunophenotyping; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D038042:Myelopoiesis / Q000502:physiology*; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D054389:Receptors, CCR1 / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C515301:Ccr1 protein, mouse; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; C503133:Gr-1 protein, mouse; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D049452:Green Fluorescent Proteins