Polarization of Macrophages in Tumor Microenvironment Using High-Throughput Single-Cell Metabolomics

作者：Xuesen Hu, Xinlin Liu, Disheng Feng, Tianrun Xu, Hang Li, Chunxiu Hu, Zhizhou Wang, Xinyu Liu, Peiyuan Yin, Xianzhe Shi, Dong Shang, Guowang Xu · 发表于：Analytical Chemistry · 年份：2024 · DOI：10.1021/acs.analchem.4c02989 · 被引用次数：11 · 研究领域：Immune cells in cancer、Epigenetics and DNA Methylation、Cancer Cells and Metastasis

Macrophages consist of a heterogeneous population of functionally distinct cells that participate in many physiological and pathological processes. They exhibit prominent plasticity by changing their different functional phenotypes represented by proinflammatory (M1) and anti-inflammatory (M2) in response to different environmental stimuli. Emerging evidence illustrates the importance of intracellular metabolic pathways in macrophage polarizations and functions. In the tumor microenvironment (TME), macrophages tend to M2 polarization, which promotes tumor growth and leads to adverse physiological effects. Due to the lack of highly specific antigens in M1 and M2 macrophages, significant challenges present in isolating these subtypes from clinical samples or in vitro coculture models of tumor-immune cells. In reverse, the single-cell technique provides the possibility to investigate the factors influencing macrophage polarization in the TME. In this research, we employed inertial microfluidic chip-mass spectrometry (IMC-MS) to conduct single-cell metabolomics analysis of macrophages polarized into the two major phenotypes, respectively, and 213 metabolites were identified in total. Subsequently, differential metabolites between macrophage phenotypes were analyzed using volcano plots and binary logistic regression models. Glutamine was pinpointed as a key metabolite for the M1 and M2 phenotypes. Experimental results from both monoculture and coculture cell models demonstrated th...