The metabolic axis of macrophage and immune cell polarization.
The metabolic axis of macrophage and immune cell polarization.
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巨噬细胞代谢轴与免疫细胞极化
DOI：
10.1242/dmm.034462
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发表时间：
2018-07-06
影响因子：
4.3
通讯作者：
Carmona-Fontaine C
中科院分区：
文献类型：
--
作者：
Hobson-Gutierrez SA;Carmona-Fontaine C
实体肿瘤的细胞外空间范围从良好培养到完全缺血，可以作为肿瘤内异质性的来源，决定恶性细胞和间质细胞的行为和分子特征。在这里，我们讨论了代谢肿瘤微环境如何调节浸润肿瘤的免疫细胞的表型，重点是肿瘤相关的巨噬细胞。这些细胞构成了一个多样化的群体，具有促肿瘤和抗炎特性，被比作抗炎的“M2”巨噬细胞。最近的研究结果表明，不同的代谢微环境如何指定巨噬细胞的一系列表型变化。在肿瘤中，细胞外代谢物水平根据与脉管系统的接近程度可预测地变化，肿瘤相关巨噬细胞和其他免疫细胞的表型变化也可预测。我们推测巨噬细胞极化的“代谢轴”调节——并被——对炎症线索的反应所调节，从而产生各种可能的表型状态。了解细胞外代谢物如何影响细胞表型使我们能够预测肿瘤相关巨噬细胞和其他肿瘤细胞可能发生的变化，目的是利用这种可预测性进行治疗。总的来说，我们描述了一个新兴的画面，其中趋化因子，生长因子和代谢肿瘤微环境共同作用，以确定肿瘤浸润免疫细胞的表型。摘要：细胞外代谢物可以介导细胞通讯，改变肿瘤细胞和正常细胞的转录和功能。本文综述了这些代谢线索如何影响免疫系统，并特别关注肿瘤相关巨噬细胞。
The extracellular space of solid tumors ranges from being well-nurtured to being completely ischemic and can serve as a source of intratumoral heterogeneity, determining the behavior and molecular profiles of malignant and stromal cells. Here, we discuss how the metabolic tumor microenvironment modulates the phenotypes of the immune cells that infiltrate tumors, with an emphasis on tumor-associated macrophages. These cells constitute a diverse population that has pro-tumoral and anti-inflammatory properties, and are likened to anti-inflammatory ‘M2’ macrophages. Recent findings show how different metabolic microenvironments specify an array of phenotypic changes in macrophages. In tumors, extracellular metabolite levels vary predictably according to proximity to the vasculature, and phenotypic changes in tumor-associated macrophages and in other immune cells are also predictable. We speculate that this ‘metabolic axis’ of macrophage polarization modulates – and is modulated by – the response to inflammatory cues, creating a wide variety of possible phenotypic states. Understanding how extracellular metabolites influence cell phenotypes allows us to predict how tumor-associated macrophages and other tumor cells might change, with the aim of harnessing this predictability for therapy. Overall, we describe an emerging picture in which chemokines, growth factors and the metabolic tumor microenvironment act together to determine the phenotypes of tumor-infiltrating immune cells. Summary: Extracellular metabolites can mediate cell communication and change transcriptional and functional aspects of tumor and normal cells. This Review focuses on how these metabolic cues affect the immune system with a special focus on tumor-associated macrophages.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1161/atvbaha.108.183319
发表时间：
2009-05-01
影响因子：
8.7
作者：
Ben-Shoshan, Jeremy;Afek, Arnon;George, Jacob
通讯作者：
George, Jacob
影响因子：
64.5
作者：
Buck MD;Sowell RT;Kaech SM;Pearce EL
通讯作者：
Pearce EL
影响因子：
5.4
作者：
Ben-Shoshan, Jeremy;Maysel-Auslender, Sophia;George, Jacob
通讯作者：
George, Jacob
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.