Laboratory of Metabolites and Proteins in Translational Research, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Department of Biotechnologies and Biosciences, Università degli Studi Milano Bicocca, Milan, Italy.
Front Immunol. 2023 Jul 12;14:1193235. doi: 10.3389/fimmu.2023.1193235. eCollection 2023.
Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients' prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype.
肿瘤相关巨噬细胞（TAMs）是肿瘤浸润免疫细胞的主要类型之一，通常分为两种功能相反的亚型，即经典激活的 M1 巨噬细胞和替代激活的 M2 巨噬细胞。TAMs 表现出不同的激活状态，可以通过巨噬细胞生物学复杂特征的两个极端来代表，即 M1 样表型（促炎活性）和 M2 样表型（抗炎活性）。基于肿瘤类型和分级，TAMs 可以获得不同的功能和特性；通常，M1 样表型是早期肿瘤阶段的典型特征，与抗肿瘤活性相关，而 M2 样表型具有促炎活性，与患者预后不良相关。基于明确刺激物将巨噬细胞分类为 M1/M2 组并不能模拟更复杂的组织环境，在这种环境中，巨噬细胞（可能来自不同的来源）会受到多种信号的不同顺序的影响。本综述旨在总结基于质谱（MS）的代谢组学在不同肿瘤中 TAMs 极化代谢修饰的最新发现。已发表的数据表明，基于 MS 的代谢组学是一种很有前途的工具，可以帮助更好地了解 TAMs 的代谢表型，尽管它在 TAMs 代谢方面的应用仍不够广泛。了解 TAMs 中的关键代谢变化是发现 TAMs 极化新生物标志物和开发针对 TAM 代谢的新型治疗方法以将 TAMs 重新极化为抗肿瘤表型的重要步骤。
