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肿瘤微环境中嗜酸性粒细胞的新曙光。

A new dawn for eosinophils in the tumour microenvironment.

机构信息

Department of Clinical Microbiology and Immunology, Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.

Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

出版信息

Nat Rev Cancer. 2020 Oct;20(10):594-607. doi: 10.1038/s41568-020-0283-9. Epub 2020 Jul 16.

Abstract

Eosinophils are evolutionarily conserved, pleotropic cells that display key effector functions in allergic diseases, such as asthma. Nonetheless, eosinophils infiltrate multiple tumours and are equipped to regulate tumour progression either directly by interacting with tumour cells or indirectly by shaping the tumour microenvironment (TME). Eosinophils can readily respond to diverse stimuli and are capable of synthesizing and secreting a large range of molecules, including unique granule proteins that can potentially kill tumour cells. Alternatively, they can secrete pro-angiogenic and matrix-remodelling soluble mediators that could promote tumour growth. Herein, we aim to comprehensively outline basic eosinophil biology that is directly related to their activity in the TME. We discuss the mechanisms of eosinophil homing to the TME and examine their diverse pro-tumorigenic and antitumorigenic functions. Finally, we present emerging data regarding eosinophils as predictive biomarkers and effector cells in immunotherapy, especially in response to immune checkpoint blockade therapy, and highlight outstanding questions for future basic and clinical cancer research.

摘要

嗜酸性粒细胞是进化上保守的、多功能的细胞,在哮喘等过敏性疾病中显示出关键的效应功能。尽管如此,嗜酸性粒细胞浸润多种肿瘤,并通过直接与肿瘤细胞相互作用或间接通过塑造肿瘤微环境(TME)来调节肿瘤进展。嗜酸性粒细胞可以对多种刺激做出快速反应,并能够合成和分泌大量分子,包括可能杀死肿瘤细胞的独特颗粒蛋白。或者,它们可以分泌促血管生成和基质重塑的可溶性介质,从而促进肿瘤生长。本文旨在全面概述与嗜酸性粒细胞在 TME 中的活性直接相关的基本嗜酸性粒细胞生物学。我们讨论嗜酸性粒细胞归巢至 TME 的机制,并研究它们在促进肿瘤发生和抗肿瘤方面的多种功能。最后,我们介绍了关于嗜酸性粒细胞作为免疫治疗中预测生物标志物和效应细胞的新兴数据,特别是针对免疫检查点阻断治疗,并强调了未来癌症基础和临床研究中的悬而未决的问题。

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