The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity
Abstract
:Simple Summary
Abstract
1. Introduction
2. Function of Tumor-Associated Macrophages (TAM) in TME
2.1. TAM in Promoting Tumor Progression
2.2. TAMs Interaction with T Cells
3. Energy Metabolism of TAMs
3.1. Glucose Metabolism of TAMs
3.2. Amino Acid Metabolism
3.3. Fatty Acid Metabolism
3.4. Tumor Acidity in Dysregulated TAM Metabolism
3.5. The Effect of TAMs Metabolism on T Lymphocytes
4. TAM Metabolism as a Target for Immunotherapy
4.1. Targeting TAM Metabolism for Improving Cancer Therapy
Drug | Target | Metabolic Effect | Disease | Effect on TAMs and TME |
---|---|---|---|---|
Metformin | AMPK (AMP-activated protein kinase) | mTOR inhibition, increased lipid breakdown, impaired glycolysis | Cancer | Decreased M2 polarization of macrophages [133,134] |
Compound 1 | Lactate DHG | Decreased lactate production, interfering TME acidity | Cancer | Increased M1/M2 ratio in TME [120] |
Methionine Sulfoximine | Glutamine Synthetase | Inhibition of glutamine metabolism, impaired glutamine usage by TAMs | Lewis Lung Carcinoma | Repolarization of M2 macrophages to M1 macrophages [70] |
Etomoxir | FAO | Impaired lipid oxidation | Cancer | Decreased M2 activity [89] |
Ranolozin | FAO | Impaired lipid oxidation | Cancer | Decreased M2 activity [89] |
CB-1158, L-Norvaline | Arginase | Inhibition of arginine synthesis, decreasing arginine levels | Solid tumors, Alzheimer’s disease | Increased anti-tumoral T cell response in TME, Repolarization of TAMs [89] |
Doxorubicin, Paclitaxel, Methodextrate | ABC Transporter | Disruption of efflux mechanism of cells leading to lipid accumulation in cells | Multidrug Resistant Cancer | Repolarization of TAMs [135] |
Pralnacasan, NCX-4016, YVAD, VAD | Caspase-1 | Decreased lipid levels in inflammatory cells | Cancer, autoimmune diseases, rheumatoid arthritis, osteoarthritis | TAMs repolarization [136] |
Rapamycin, RAD001 | mTOR | Decreased synthesis of proteins and nucleic acids | Amyotrophic lateral sclerosis, Glioma, Non-small cell lung cancer | Repolarization of TAMs [137] |
PHGDH inhibitors | Phosphoglycerate dehydrogenase | Disruption of serine synthesis | Breast cancer, lung cancer, malign melanoma | Increased anti-tumoral T cell response in TME [138,139,140] |
2-deoxyglucose (2-DG) | Hexokinase 2 | Aerobic glycolysis inhibition by effecting the first step of glycolysis | Cancer | Repolarization of TAMs [141] |
CB-839 | Glutaminase-1 | Negative effect on glutamine metabolism | Breast Cancer | Decreased glutamate levels in TME [142,143] |
4.2. Na+/H+ Exchanger (NHE1) as a Modulator of TAM Metabolism and Immune Checkpoint Therapy
4.3. Targeting TAM Metabolism to Improve Immune Checkpoint Therapy
4.4. Effect of Tumor Acidity on the Activity of Therapeutic Antibodies
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Hasan, M.N.; Capuk, O.; Patel, S.M.; Sun, D. The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity. Cancers 2022, 14, 3331. https://doi.org/10.3390/cancers14143331
Hasan MN, Capuk O, Patel SM, Sun D. The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity. Cancers. 2022; 14(14):3331. https://doi.org/10.3390/cancers14143331
Chicago/Turabian StyleHasan, Md Nabiul, Okan Capuk, Shivani M. Patel, and Dandan Sun. 2022. "The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity" Cancers 14, no. 14: 3331. https://doi.org/10.3390/cancers14143331