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Polarization of Macrophages in Tumor Microenvironment Using High-Throughput Single-Cell Metabolomics
Xuesen Hu1,2,3, Xinlin Liu4, Disheng Feng1,2,3
1CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Analytical Chemistry
|September 2, 2024
Summary
Glutamine is crucial for M1 macrophage polarization in the tumor microenvironment. This study used single-cell metabolomics to show glutamine availability impacts M1 vs. M2 macrophage balance, offering new cancer therapy targets.
Area of Science:
- Immunology
- Metabolomics
- Cancer Biology
Background:
- Macrophages are key immune cells with plastic phenotypes (M1/M2) influencing disease.
- Intracellular metabolism significantly impacts macrophage polarization and function.
- Tumor-associated macrophages often adopt an M2 phenotype, promoting tumor progression.
Purpose of the Study:
- To investigate the role of intracellular metabolites in macrophage polarization within the tumor microenvironment.
- To identify key metabolic factors influencing M1 and M2 macrophage phenotypes using single-cell analysis.
- To explore glutamine's specific role in macrophage polarization and its therapeutic potential in cancer.
Main Methods:
- Single-cell metabolomics analysis using inertial microfluidic chip-mass spectrometry (IMC-MS).
- Identification and quantification of 213 metabolites in polarized M1 and M2 macrophages.
- Statistical analysis including volcano plots and binary logistic regression to identify differential metabolites.
Main Results:
- Glutamine was identified as a critical metabolite distinguishing M1 and M2 macrophage phenotypes.
- M1 macrophage polarization demonstrated a higher dependency on glutamine compared to M2 polarization.
- Glutamine deficiency impaired M1 polarization, while glutamine replenishment enhanced M1 polarization and suppressed tumor cell growth in coculture models.
Conclusions:
- Glutamine is a key metabolic regulator of macrophage polarization in the tumor microenvironment.
- Targeting glutamine metabolism presents a promising therapeutic strategy for modulating anti-tumor immunity.
- Single-cell metabolomics provides novel insights into the metabolic underpinnings of immune cell function in cancer.
