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肿瘤相关巨噬细胞的代谢:与肿瘤微环境的相互作用。

Metabolism in tumour-associated macrophages: a with the tumour microenvironment.

机构信息

Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany.

These authors contributed equally.

出版信息

Eur Respir Rev. 2020 Oct 1;29(157). doi: 10.1183/16000617.0134-2020. Print 2020 Sep 30.

Abstract

Lung cancer is the leading cause of death from cancer worldwide. Recent studies demonstrated that the tumour microenvironment (TME) is pivotal for tumour progression, providing multiple targeting opportunities for therapeutic strategies. As one of the most abundant stromal cell types in the TME, tumour-associated macrophages (TAMs) exhibit high plasticity. Malignant cells alter their metabolic profiles to adapt to the limited availability of oxygen and nutrients in the TME, resulting in functional alteration of TAMs. The metabolic features of TAMs are strongly associated with their functional plasticity, which further impacts metabolic profiling in the TME and contributes to tumourigenesis and progression. Here, we review the functional determination of the TME by TAM metabolic alterations, including glycolysis as well as fatty acid and amino acid metabolism, which in turn are influenced by environmental changes. Additionally, we discuss metabolic reprogramming of TAMs to a tumouricidal phenotype as a potential antitumoural therapeutic strategy.

摘要

肺癌是全球癌症死亡的主要原因。最近的研究表明,肿瘤微环境(TME)对肿瘤的进展至关重要,为治疗策略提供了多种靶向机会。作为 TME 中最丰富的基质细胞类型之一,肿瘤相关巨噬细胞(TAM)表现出高度的可塑性。恶性细胞改变其代谢谱以适应 TME 中氧气和营养物质的有限可用性,导致 TAM 的功能改变。TAM 的代谢特征与其功能可塑性密切相关,这进一步影响 TME 中的代谢特征,并有助于肿瘤发生和进展。在这里,我们综述了 TAM 代谢改变对 TME 功能的决定作用,包括糖酵解以及脂肪酸和氨基酸代谢,而这些又受到环境变化的影响。此外,我们还讨论了 TAM 的代谢重编程为肿瘤杀伤表型作为一种潜在的抗肿瘤治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f31a/9488699/275635ef2fbc/ERR-0134-2020.01.jpg

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