Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard, USA.
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard, USA; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Switzerland; AGORA Cancer Research Center, Lausanne, Switzerland; Swiss Cancer Center Leman, Lausanne and Geneva, Switzerland; Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Center for Translational Research in Onco-Hematology, University of Geneva, Switzerland.
Semin Immunol. 2021 Oct;57:101538. doi: 10.1016/j.smim.2021.101538. Epub 2021 Dec 4.
Neutrophils have historically been considered a singular, terminally-differentiated cell population, replete with pre-formed granules, poised to react quickly, aggressively, and somewhat non-specifically in the face of a microbial challenge or tissue injury. However, in recent years, neutrophil biologists have started revisiting this simplistic conception. Many studies have identified complexities in neutrophil biology, and these findings have led the field to redefine neutrophil heterogeneity from multiple angles including their development and maturation, their tissue location, and their ability to respond to various (pathological) stimuli. In this review, we discuss the importance of this reassessment within the context of cancer. Experimental evidence supports that neutrophil behavior is diverse, context-dependent, and manipulable; cutting-edge technologies have enabled the identification of neutrophil heterogeneity with high resolution and in an unbiased manner, revealing what may be critical underpinnings of these diverse behaviors, and enabling sophisticated computational assessments of specific programs and interactions. We are coming ever closer to delineating a holistic picture of neutrophil heterogeneity and how it may interplay with cancer stage, tumor microenvironment, and therapy. All of this together paints a promising picture when considering how clinical practice may harness the heterogeneity of these cells, for biomarkers or therapeutic approaches, leveraging what we are learning about these powerful and plentiful immune effectors.
中性粒细胞在过去一直被认为是一种单一的、终末分化的细胞群体，充满了预先形成的颗粒，随时准备在面对微生物挑战或组织损伤时迅速、积极且有些非特异性地反应。然而，近年来，中性粒细胞生物学家开始重新审视这一简单的概念。许多研究已经确定了中性粒细胞生物学的复杂性，这些发现促使该领域从多个角度重新定义中性粒细胞异质性，包括它们的发育和成熟、它们在组织中的位置以及它们对各种（病理）刺激的反应能力。在这篇综述中，我们讨论了在癌症背景下重新评估这一概念的重要性。实验证据支持中性粒细胞行为是多样化的、依赖于背景的且可操纵的；先进的技术使我们能够以高分辨率和无偏倚的方式识别中性粒细胞异质性，揭示这些不同行为的关键基础，并能够对特定程序和相互作用进行复杂的计算评估。我们越来越接近于描绘出中性粒细胞异质性的全貌，以及它如何与癌症分期、肿瘤微环境和治疗相互作用。所有这些都为临床实践如何利用这些细胞的异质性提供了有希望的前景，无论是用于生物标志物还是治疗方法，都可以利用我们对这些强大而丰富的免疫效应细胞的了解。
