Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice
Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice
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DOI：
10.1182/blood-2008-01-136895
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发表时间：
2008-06-15
期刊：
影响因子：
20.3
通讯作者：
Matsushima, Kouji
中科院分区：
文献类型：
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作者：
Sawanobori, Yasushi;Ueha, Satoshi;Matsushima, Kouji
肿瘤生长与异常骨髓生成相关，包括具有促进肿瘤生长潜力的CD 11 B（+）Gr-1（+）髓源性抑制细胞（MDSC）的蓄积。然而，肿瘤相关MDSC的身份，生长和迁移仍然不确定。我们在此证明，肿瘤部位的MDSC主要由骨髓来源的CD 11b（+）Gr-1（hi）Ly-6C（int）中性粒细胞和CD 11b（+）Gr- 1（int/dull）Ly-6C（hi）巨噬细胞组成。出乎意料的是，在体内溴脱氧尿苷（BrdU）标记和共生实验表明，肿瘤浸润巨噬细胞比中性粒细胞更迅速地补充。CCR 2缺陷引起肿瘤中浸润细胞优势从巨噬细胞向中性粒细胞的显著转化，肿瘤中CXCR 2配体和粒细胞集落刺激因子的过量产生，而不影响肿瘤生长。总体而言，我们的数据建立了MDSC的身份和动力学在荷瘤宿主介导的趋化因子和阐明了意想不到的影响，缺乏巨噬细胞对肿瘤的发展。
Tumor growth is associated with aberrant myelopoiesis, including the accumulation of CD11 b(+)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.