Institute of Pulmonary Medicine, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Carcinogenesis. 2012 May;33(5):949-55. doi: 10.1093/carcin/bgs123. Epub 2012 Mar 16.
Neutrophils play an established role in host defense and in killing invading microorganisms. Although neutrophils are traditionally considered in the context of their antibacterial functions, it is becoming increasingly clear that tumor-associated neutrophils (TAN) play a major role in cancer biology. Neutrophils make up a significant portion of the inflammatory cell infiltrate in many models of cancer. Like all other leukocytes, they move into tissues under the influence of specific chemokines, cytokines and cell adhesion molecules. The tumor microenvironment has been shown to be responsible for their recruitment in cancer. We have found that TAN are a distinct population of neutrophils, differing markedly in their transcriptomic profile from both naive neutrophils and the granulocytic fraction of myeloid-derived suppressor cells. Studies have demonstrated specific examples of tumor-mediated signals (such as transforming growth factor-β) that induce the formation of a pro-tumorigenic (N2) phenotype capable of supporting tumor growth and suppressing the antitumor immune response. However, there are also studies showing that TAN can also have an antitumorigenic (N1) phenotype. Herein, we explore the literature on the different mechanisms of TAN recruitment to tumors, the unique characteristics of TAN and what shapes their pro- and/or antitumor effects.
中性粒细胞在宿主防御和杀死入侵的微生物方面发挥着既定的作用。尽管中性粒细胞传统上被认为具有抗菌功能，但越来越明显的是，肿瘤相关中性粒细胞（TAN）在癌症生物学中起着重要作用。中性粒细胞构成了许多癌症模型中炎症细胞浸润的重要组成部分。与所有其他白细胞一样，它们在特定趋化因子、细胞因子和细胞黏附分子的影响下迁移到组织中。肿瘤微环境被证明是其在癌症中募集的原因。我们发现 TAN 是中性粒细胞的一个独特群体，其转录组谱与幼稚中性粒细胞和髓源性抑制细胞的粒细胞部分明显不同。研究已经证实了肿瘤介导的信号（如转化生长因子-β）的具体例子，这些信号诱导形成一种促肿瘤（N2）表型，能够支持肿瘤生长并抑制抗肿瘤免疫反应。然而，也有研究表明，TAN 也可以具有抗肿瘤（N1）表型。本文探讨了 TAN 向肿瘤募集的不同机制、TAN 的独特特征以及形成其促肿瘤和/或抗肿瘤作用的因素。
