N1 versus N2 and PMN-MDSC: 对肿瘤相关中性粒细胞当前概念的重要评估以及人类肿瘤学的新方向。
N1 versus N2 and PMN-MDSC: A critical appraisal of current concepts on tumor-associated neutrophils and new directions for human oncology.
发表日期:2022 Dec 11
作者:
Benedict Boateng Antuamwine, Rebeka Bosnjakovic, Francisca Hofmann-Vega, Xi Wang, Theodosios Theodosiou, Ioannis Iliopoulos, Sven Brandau
来源:
IMMUNOLOGICAL REVIEWS
摘要:
肿瘤相关中性粒细胞(TAN)的研究目前蓬勃发展,这是因为中性粒细胞浸润到肿瘤组织中与临床实践极为相关。这种相关性在大多数人类癌症中,高频率的肿瘤内中性粒细胞与不良预后之间存在强烈的相关性。近期对小鼠中性粒细胞进行的高维分析提供了关于中性粒细胞在小鼠癌症和其他非恶性炎症疾病模型中意想不到的可塑性证据。新的分析工具使我们能够更深入地了解中性粒细胞的分化和成熟过程。这些技术和科学的发展导致对疾病小鼠模型和最近也包括人类中越来越多的不同转录状态和相关表型的描述。目前,在癌症中对这些不同的转录状态和潜在表型的功能验证还不足。目前,有关癌症中中性粒细胞的功能概念主要依赖于髓系源性抑制细胞(MDSC)概念和二分的简单N1-N2范式。在本文中,我们回顾了这些概念的历史发展,从我们自己的工作背景出发,进行了批判性评估,并提出了建议,以便促进TAN研究从实验认识到临床转化。© 2022 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.
Research on tumor-associated neutrophils (TAN) currently surges because of the well-documented strong clinical relevance of tumor-infiltrating neutrophils. This relevance is illustrated by strong correlations between high frequencies of intratumoral neutrophils and poor outcome in the majority of human cancers. Recent high-dimensional analysis of murine neutrophils provides evidence for unexpected plasticity of neutrophils in murine models of cancer and other inflammatory non-malignant diseases. New analysis tools enable deeper insight into the process of neutrophil differentiation and maturation. These technological and scientific developments led to the description of an ever-increasing number of distinct transcriptional states and associated phenotypes in murine models of disease and more recently also in humans. At present, functional validation of these different transcriptional states and potential phenotypes in cancer is lacking. Current functional concepts on neutrophils in cancer rely mainly on the myeloid-derived suppressor cell (MDSC) concept and the dichotomous and simple N1-N2 paradigm. In this manuscript, we review the historic development of those concepts, critically evaluate these concepts against the background of our own work and provide suggestions for a refinement of current concepts in order to facilitate the transition of TAN research from experimental insight to clinical translation.© 2022 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.