Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
PLoS One. 2012;7(2):e31524. doi: 10.1371/journal.pone.0031524. Epub 2012 Feb 14.
The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC) that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN) are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN) and to the granulocytic fraction of MDSC (G-MDSC).In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst) were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes), and cytokines (e.g. TNF-α, IL-1-α/β), were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages.This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.
髓系细胞在支持肿瘤生长中的作用已得到充分证实。大多数研究都集中在肿瘤负荷动物中积累的髓系来源的抑制细胞（MDSC）上，但也已知肿瘤相关中性粒细胞（TAN）能够增强肿瘤生长。然而，对于它们的进化、表型以及与幼稚中性粒细胞（NN）和 MDSC 的粒性部分（G-MDSC）的关系，人们知之甚少。在本研究中，使用转录组学方法在小鼠中比较了这些细胞类型。我们的数据表明，这三种中性粒细胞群体在其 mRNA 谱上存在显著差异，NN 和 G-MDSC 彼此之间的关系比 TAN 更为密切。结构基因和与细胞细胞毒性（即呼吸爆发）相关的基因在 TAN 中显著下调。相比之下，许多免疫相关基因和途径，包括与抗原呈递复合物（例如，所有六个 MHC-II 复合物基因）和细胞因子（例如 TNF-α、IL-1-α/β）相关的基因，在 G-MDSC 中上调，在 TAN 中进一步上调。在 TAN 中，与 NN 相比，测试的 25 种趋化因子中有 13 种明显上调，包括对 T/B 细胞、中性粒细胞和巨噬细胞的趋化剂的显著上调。本研究描述了与癌症相关的不同中性粒细胞群体，指出了 TAN 与其他中性粒细胞群体之间的主要差异。
