Glucose Metabolism: The Metabolic Signature of Tumor Associated Macrophage

Zhang, Qi; Wang, Junli; Yadav, Dipesh Kumar; Bai, Xueli

doi:10.3389/fimmu.2021.702580

Cited by 34 publications

(32 citation statements)

References 103 publications

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“…However, hyperglycemia can lead to increased concentrations of glucose in EBF and can mask glucose consumption during inflammation in the affected body compartment [15,16]. Furthermore, the generally accepted scheme of glucose metabolism indicates that the concentration of lactate in EBF is not influenced exclusively by the extent of anaerobic metabolism in EBF but also by the supply of the energy substrate, i.e., glucose (Figure 1) [17][18][19]. Neutrophils are the principal cells of innate immunity.…”

Section: Introductionmentioning

confidence: 99%

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage

Kelbich

Vachata

Malý

et al. 2022

Life

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The simultaneous cytological and metabolic investigation of various extravascular body fluids (EBFs) provides clinically relevant information about the type and intensity of the immune response in particular organ systems. The oxidative burst of professional phagocytes with the concomitant production of reactive oxygen species consumes a large amount of oxygen and is the cause of switch to the development of anaerobic metabolism. We assessed the relationships between percentages of neutrophils, aerobic and anaerobic metabolism, and tissue damage via the determination of aspartate aminotransferase catalytic activities (AST) in cerebrospinal fluid (CSF), pleural effusions (PE), abdominal effusions (AE), and synovial fluids (SF). EBFs with 0.0–20.0% neutrophils: 83.0% aerobic and 1.3% strongly anaerobic cases with median of AST = 13.8 IU/L in CSF; 68.0% aerobic and 9.0% strongly anaerobic cases with median of AST = 20.4 IU/L in PE; 77.5% aerobic and 10.5% strongly anaerobic cases with median of AST = 18.0 IU/L in AE; 64.1% aerobic and 7.7% strongly anaerobic cases with median of AST = 13.8 IU/L in SF. EBFs with 80.0–100.0% neutrophils: 4.2% aerobic and 73.7% strongly anaerobic cases with median of AST = 19.2 IU/L in CSF; 7.4% aerobic and 77.3% strongly anaerobic cases with median of AST = 145.2 IU/L in PE; 11.8% aerobic and 73.7% strongly anaerobic cases with median of AST = 61.8 IU/L in AE; 25.5% aerobic and 38.2% strongly anaerobic cases with median of AST = 37.2 IU/L in SF. The significant presence of neutrophils, concomitant strong anaerobic metabolism, and elevated AST in various EBFs are reliable signs of damaging purulent inflammation.

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Section: Introductionmentioning

confidence: 99%

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage

Kelbich

Vachata

Malý

et al. 2022

Life

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“…Diabetes is a chronic disease that is characteried by impaired glucose metabolism. This condition can easily cause microvascular and macrovascular complications due to high glucoselevels that can easily active the immune system [ 28 , 29 ], especially the activation of macrophages [ 30 ]. Based on our previous reports on miR-32 in coronary artery calcification and microglia [ 7 , 8 ], this study further explored the roles and mechanisms by which miR-32 acts in the process of macrophage-regulated T2D VC.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

Cao

Chen

et al. 2022

J Transl Med

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Background The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear. Methods Wild-type (WT) and miR-32−/− mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32−/− mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy. Results We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32−/− mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32−/− mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells. Conclusions These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs.

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“…The metabolism of TAMs is highly heterogeneous not only within different TAM populations, but also among similar TAM populations which, at least in part, explains the failure or sub-optimal efficacies of TAM-directed therapeutic approaches and immune checkpoint blockade therapies [ 154 , 155 ]. Pro-tumoral M2 macrophages secrete anti-inflammatory cytokines such as IL-10 and TGF-Beta to block the anti-tumoral T cell response against tumoral cells [ 156 ]. Inflammatory M1-activated macrophages utilize the glycolytic metabolism for their function [ 124 ] and the PKM2 in macrophages enables the metabolic shifts of the macrophages from OXPHOS to glycolysis.…”

Section: Tam Metabolism As a Target For Immunotherapymentioning

confidence: 99%

The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity

Hasan

Capuk

Patel

et al. 2022

Cancers

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Cancer cells possess a high metabolic demand for their rapid proliferation, survival, and progression and thus create an acidic and hypoxic tumor microenvironment (TME) deprived of nutrients. Moreover, acidity within the TME is the central regulator of tumor immunity that influences the metabolism of the immune cells and orchestrates the local and systemic immunity, thus, the TME has a major impact on tumor progression and resistance to anti-cancer therapy. Specifically, myeloid cells, which include myeloid-derived suppressor cells (MDSC), dendritic cells, and tumor-associated macrophages (TAMs), often reprogram their energy metabolism, resulting in stimulating the angiogenesis and immunosuppression of tumors. This review summarizes the recent findings of glucose, amino acids, and fatty acid metabolism changes of the tumor-associated macrophages (TAMs), and how the altered metabolism shapes the TME and anti-tumor immunity. Multiple proton pumps/transporters are involved in maintaining the alkaline intracellular pH which is necessary for the glycolytic metabolism of the myeloid cells and acidic TME. We highlighted the roles of these proteins in modulating the cellular metabolism of TAMs and their potential as therapeutic targets for improving immune checkpoint therapy.

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Glucose Metabolism: The Metabolic Signature of Tumor Associated Macrophage

Cited by 34 publications

References 103 publications

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity

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