肿瘤相关中性粒细胞的悖论:用细胞毒性物质为肿瘤生长提供燃料。
The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances.
机构信息
Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
出版信息
Cell Cycle. 2010 May;9(9):1732-7. doi: 10.4161/cc.9.9.11297. Epub 2010 May 25.
Human cancers are comprised of numerous cell types including neutrophils. Although often ignored, neutrophils are frequently present at sites of tumorigenesis including the kidney, breast, colon and lung. These cells possess substances such as reactive oxygen species and proteinases that are capable of modifying tumor growth and invasiveness. This review addresses recent reports describing both pro-host and pro-tumor roles for neutrophils and neutrophil-derived substances and will examine the alterations in neutrophil behavior that explain this apparent biological discrepancy. Unfortunately, with the exception of investigator driven manipulation of neutrophil function, these cells function overwhelmingly against the host in the setting of cancer. Many cancers are capable of recruiting neutrophils to sites of tumorigenesis where they enhance tumor growth. Identification of the neutrophil-derived substances that promote tumor growth may yield novel therapeutic approaches to inhibit cancer progression. Alternatively, strategies designed to generate highly activated and cytotoxic neutrophils within the tumor microenvironment may provide a means to unleash the tumoricidal potential of the host's innate immune response.
人类癌症由包括中性粒细胞在内的多种细胞类型组成。尽管经常被忽视,但中性粒细胞经常存在于肿瘤发生的部位,包括肾脏、乳房、结肠和肺。这些细胞具有活性氧物质和蛋白酶等物质,能够改变肿瘤的生长和侵袭性。本综述介绍了最近描述中性粒细胞及其衍生物质对宿主和肿瘤的有利作用的报告,并将检查解释这种明显生物学差异的中性粒细胞行为的改变。不幸的是,除了研究人员对中性粒细胞功能的主动操纵外,在癌症环境中,这些细胞绝大多数对宿主不利。许多癌症能够招募中性粒细胞到肿瘤发生部位,从而促进肿瘤生长。鉴定促进肿瘤生长的中性粒细胞衍生物质可能会产生抑制癌症进展的新的治疗方法。或者,设计在肿瘤微环境中产生高度激活和细胞毒性的中性粒细胞的策略可能提供一种释放宿主固有免疫反应的抗肿瘤潜力的方法。