Neutrophils in the Tumor Microenvironment.

文献信息

DOI	10.1016/j.it.2015.11.008
PMID	26700397
期刊	Trends in immunology
影响因子	13.9
JCR 分区	Q1
发表年份	2016
被引次数	321
关键词	中性粒细胞, 肿瘤微环境, 慢性炎症, 癌症进展
文献类型	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN	1471-4906
页码	41-52
期号	37(1)
作者	Davalyn R Powell, Anna Huttenlocher

一句话小结

本研究回顾了中性粒细胞在急性组织损伤、感染及肿瘤微环境中的作用，强调其在慢性炎症背景下的持续存在可能与癌症进展相关。通过探讨中性粒细胞的招募和消退机制，研究揭示了其在肿瘤微环境中可能支持或抑制癌症进展的双重角色，指出了当前理解中的空白和未来研究的重要方向。

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中性粒细胞 · 肿瘤微环境 · 慢性炎症 · 癌症进展

摘要

中性粒细胞是急性组织损伤和感染部位的第一响应者。最近的研究表明，除了中性粒细胞凋亡，伤口处中性粒细胞炎症的消退还可以通过从组织反向迁移和重新穿越到血管中来介导。在慢性炎症的环境中，中性粒细胞在组织中持续存在，这种持续性与癌症进展有关。然而，中性粒细胞在肿瘤微环境中的作用仍存在争议，既有支持肿瘤的证据，也有抑制肿瘤的证据。在此，我们回顾了调节中性粒细胞招募和在组织损伤部位消退的机制，特别关注肿瘤微环境。我们讨论了目前对中性粒细胞如何改变肿瘤微环境以支持或阻碍癌症进展的理解，并在此背景下概述了理解中的空白和重要的研究领域。

英文摘要

Neutrophils are the first responders to sites of acute tissue damage and infection. Recent studies suggest that in addition to neutrophil apoptosis, resolution of neutrophil inflammation at wounds can be mediated by reverse migration from tissues and transmigration back into the vasculature. In settings of chronic inflammation, neutrophils persist in tissues, and this persistence has been associated with cancer progression. However, the role of neutrophils in the tumor microenvironment remains controversial, with evidence for both pro- and anti-tumor roles. Here we review the mechanisms that regulate neutrophil recruitment and resolution at sites of tissue damage, with a specific focus on the tumor microenvironment. We discuss the current understanding as to how neutrophils alter the tumor microenvironment to support or hinder cancer progression, and in this context outline gaps in understanding and important areas of inquiry.

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主要研究问题

核心洞察

研究背景和目的

中性粒细胞是最早响应急性组织损伤和感染的白细胞类型，近年来的研究表明它们在肿瘤微环境中的作用仍然存在争议。中性粒细胞既可以促进肿瘤进展，也可以发挥抗肿瘤作用。本文综述了中性粒细胞在组织损伤和肿瘤微环境中的招募和消退机制，探讨它们如何影响癌症进展，并指出当前理解中的不足和未来研究方向。

主要方法/材料/实验设计

研究主要采用小鼠和斑马鱼模型，分析中性粒细胞在组织损伤和肿瘤微环境中的行为和作用。通过观察中性粒细胞的招募、极化、相互作用和逆向迁移，揭示其在炎症和肿瘤中的双重角色。

关键结果和发现

中性粒细胞的招募：中性粒细胞通过化学因子（如CXCL1、CXCL2等）被招募到肿瘤和损伤部位。
极化现象：中性粒细胞可以根据微环境的信号极化为促肿瘤(N2)或抗肿瘤(N1)表型，前者与肿瘤进展相关，后者则可能促进免疫反应。
肿瘤相关中性粒细胞(TANs)：TANs的存在与多种癌症的差劲预后相关，可能通过释放MMP9等因子促进肿瘤血管生成和转移。
逆向迁移机制：中性粒细胞能够通过逆向迁移回到血液循环，这一过程对于炎症的消退至关重要。

主要结论/意义/创新性

中性粒细胞在肿瘤微环境中扮演复杂角色，既可促进肿瘤进展，也可能参与抗肿瘤免疫。了解中性粒细胞的极化和逆向迁移机制，可能为癌症治疗提供新的靶点，特别是在设计能够促进中性粒细胞逆向迁移以减少肿瘤炎症的疗法方面。

研究局限性和未来方向

机制研究不足：关于中性粒细胞如何在不同类型的肿瘤中发挥作用的机制仍不清晰。
模型系统的局限性：虽然小鼠和斑马鱼模型提供了有价值的见解，但仍需更多临床研究验证。
未来研究方向：需探索中性粒细胞极化的调控机制，及其在不同肿瘤阶段的作用，进一步明确它们在癌症中的潜在治疗应用。

总结

中性粒细胞在癌症中的作用复杂且多样，理解其在肿瘤微环境中的行为和机制对于开发新型癌症治疗策略至关重要。未来的研究应关注中性粒细胞的极化和逆向迁移，以期为癌症免疫治疗提供新的思路。

参考文献

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IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment. - Luciana Benevides;Denise Morais da Fonseca;Paula Barbim Donate;Daniel Guimarães Tiezzi;Daniel D De Carvalho;Jurandyr M de Andrade;Gislaine A Martins;João S Silva - Cancer research (2015)
Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. - Luke Pase;Judith E Layton;Christine Wittmann;Felix Ellett;Cameron J Nowell;Constantino Carlos Reyes-Aldasoro;Sony Varma;Kelly L Rogers;Chris J Hall;M Cristina Keightley;Philip S Crosier;Clemens Grabher;Joan K Heath;Stephen A Renshaw;Graham J Lieschke - Current biology : CB (2012)
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A Strong Neutrophil Elastase Proteolytic Fingerprint Marks the Carcinoma Tumor Proteome. - Michał Kistowski;Janusz Dębski;Jakub Karczmarski;Agnieszka Paziewska;Jacek Olędzki;Michał Mikula;Jerzy Ostrowski;Michał Dadlez - Molecular & cellular proteomics : MCP (2017)

... (311 更多篇文献)

Neutrophils in the Tumor Microenvironment. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

总结 ​

参考文献 ​

引用本文的文献 ​