Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
Cell Rep. 2015 Feb 3;10(4):562-73. doi: 10.1016/j.celrep.2014.12.039. Epub 2015 Jan 22.
Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.
中性粒细胞在癌症中的功能存在争议，因为已经证明中性粒细胞既具有促进肿瘤的功能，也具有抗肿瘤的功能。我们鉴定出一种异质性的低密 度中性粒细胞亚群（LDNs），其在自限性炎症中短暂出现，但随着癌症的进展持续积累。LDNs 表现出受损的中性粒细胞功能和免疫抑制特性，这些特性与成熟、高密度中性粒细胞（HDNs）形成鲜明对比。LDNs 由不成熟的髓系来源的抑制细胞（MDSCs）和成熟细胞组成，这些成熟细胞是通过 TGF-β 依赖性机制从 HDNs 衍生而来的。我们的研究结果鉴定出循环中性粒细胞的三个不同群体，并挑战了成熟中性粒细胞可塑性有限的概念。此外，我们的研究结果提供了一种机制解释，以减轻中性粒细胞在癌症中功能的争议。
