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In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
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Macrophages are metabolically heterogeneous within the tumor microenvironment.
Xenia Geeraerts1, Juan Fernández-Garcia2, Felix J Hartmann3
1Laboratory of Myeloid Cell Immunology, VIB Center for Inflammation Research, Brussels 1050, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium.
Cell Reports
|December 29, 2021
Summary
Tumor-associated macrophages (TAMs) have distinct metabolic profiles. Pro-inflammatory TAMs show impaired TCA cycle function, while reparative TAMs utilize lactate for energy and enhance their T-cell suppressive abilities.
Area of Science:
- Immunology
- Cancer Biology
- Metabolic Research
Background:
- Macrophages, particularly tumor-associated macrophages (TAMs), are key components of the tumor microenvironment.
- Distinct TAM subsets can influence tumor progression, but their metabolic characteristics are not well understood.
Purpose of the Study:
- To investigate the metabolic differences between pro-inflammatory (MHC-IIhi) and reparative (MHC-IIlo) TAM subsets.
- To determine the role of lactate in regulating TAM metabolism and function.
Main Methods:
- Transcriptomic analysis of TAM subsets.
- Metabolic assays to assess cellular respiration and glycolysis.
- Investigation of lactate exchange and utilization by TAMs.
Main Results:
- Pro-inflammatory MHC-IIhi TAMs exhibit a hampered tricarboxylic acid (TCA) cycle.
- Reparative MHC-IIlo TAMs display higher oxidative and glycolytic metabolism.
- MHC-IIlo TAMs utilize lactate as a carbon source, which supports their oxidative metabolism and enhances T-cell suppressive capacity, while lactate decreases MHC-IIhi TAM metabolic activity.
Conclusions:
- Distinct TAM subsets possess unique metabolic profiles.
- Lactate acts as both a carbon source and a regulator of TAM metabolism and function, influencing T-cell suppression.
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