We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be controlled by the down-regulation of Rb1, but not IRF8, which is known to regulate the expansion of PMN-MDSCs from classic granulocyte precursors. In cancer patients, putative MLPGs were found within the population of CXCR1+CD15-CD14+HLA-DR-/lo monocytic cells. These findings describe a mechanism of abnormal myelopoiesis in cancer and suggest potential new approaches for selective targeting of MDSCs.

中文翻译：

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鉴定癌症中粒细胞的单核细胞样前体是PMN-MDSC积累的机制。

我们已经确定了在体外和体内分化为粒细胞但仍属于单核细胞谱系的前体。我们将这些细胞称为粒细胞（MLPG）的单核细胞样前体。在稳定状态下，脾脏中不存在MLPG，而在骨髓（BM）中则几乎检测不到。相比之下，这些细胞在荷瘤小鼠中显着扩增，并分化为多形核髓样来源的抑制细胞（PMN-MDSCs）。选择性清除单核细胞对幼稚小鼠的粒细胞数量没有影响，但是使荷瘤小鼠的PMN-MDSC种群减少了50％。发现MLPGs的扩增受Rb1的下调控制，但不受IRF8的控制，IRF8可以调节经典粒细胞前体对PMN-MDSCs的扩增。在癌症患者中 在CXCR1 + CD15-CD14 + HLA-DR- / lo单核细胞群中发现了推定的MLPG。这些发现描述了癌症中异常骨髓生成​​的机制，并提出了选择性靶向MDSC的潜在新方法。