Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells
Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the eff...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3489 |
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| author | Lea Katharina Picard Elisabeth Littwitz-Salomon Herbert Waldmann Carsten Watzl |
| author_facet | Lea Katharina Picard Elisabeth Littwitz-Salomon Herbert Waldmann Carsten Watzl |
| author_sort | Lea Katharina Picard |
| collection | DOAJ |
| description | Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances. |
| first_indexed | 2024-03-09T19:11:40Z |
| format | Article |
| id | doaj.art-c3614347d4894c15a017f4988b791595 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:40Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c3614347d4894c15a017f4988b7915952023-11-24T04:09:35ZengMDPI AGCells2073-44092022-11-011121348910.3390/cells11213489Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK CellsLea Katharina Picard0Elisabeth Littwitz-Salomon1Herbert Waldmann2Carsten Watzl3Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), D-44139 Dortmund, GermanyInstitute for Virology, University Hospital Essen, D-45147 Essen, GermanyMax Planck Institute of Molecular Physiology, D-44227 Dortmund, GermanyDepartment for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), D-44139 Dortmund, GermanyTumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances.https://www.mdpi.com/2073-4409/11/21/3489natural killer cellsglucose transportermetabolismdegranulationcytokines |
| spellingShingle | Lea Katharina Picard Elisabeth Littwitz-Salomon Herbert Waldmann Carsten Watzl Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells Cells natural killer cells glucose transporter metabolism degranulation cytokines |
| title | Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells |
| title_full | Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells |
| title_fullStr | Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells |
| title_full_unstemmed | Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells |
| title_short | Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells |
| title_sort | inhibition of glucose uptake blocks proliferation but not cytotoxic activity of nk cells |
| topic | natural killer cells glucose transporter metabolism degranulation cytokines |
| url | https://www.mdpi.com/2073-4409/11/21/3489 |
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