Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells
Energy metabolism is key to the promotion of tumor growth, development, and metastasis. At the same time, cellular metabolism also mediates immune cell survival, proliferation and cytotoxic responses within the tumor microenvironment. The ability of natural killer cells to eradicate tumors relies on...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02517/full |
| _version_ | 1811333232284663808 |
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| author | Andrea M. Chambers Kyle B. Lupo Sandro Matosevic Sandro Matosevic |
| author_facet | Andrea M. Chambers Kyle B. Lupo Sandro Matosevic Sandro Matosevic |
| author_sort | Andrea M. Chambers |
| collection | DOAJ |
| description | Energy metabolism is key to the promotion of tumor growth, development, and metastasis. At the same time, cellular metabolism also mediates immune cell survival, proliferation and cytotoxic responses within the tumor microenvironment. The ability of natural killer cells to eradicate tumors relies on their ability to functionally persist for the duration of their anti-tumor effector activity. However, a tumor's altered metabolic requirements lead to compromised functional responses of cytokine-activated natural killer cells, which result in decreased effectiveness of adoptive cell-based immunotherapies. Tumors exert these immunosuppressive effects through a number of mechanisms, a key driver of which is hypoxia. Hypoxia also fuels the generation of adenosine from the cancer-associated ectoenzymes CD39 and CD73. Adenosine's immunosuppression manifests in decreased proliferation and impaired anti-tumor function, with adenosinergic signaling emerging as an immunometabolic checkpoint blockade target. Understanding such immunometabolic suppression is critical in directing the engineering of a new generation of natural killer cell-based immunotherapies that have the ability to more effectively target difficult-to-treat solid tumors. |
| first_indexed | 2024-04-13T16:48:52Z |
| format | Article |
| id | doaj.art-f078505dfdb0495285c983ceab5b7282 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T16:48:52Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f078505dfdb0495285c983ceab5b72822022-12-22T02:39:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02517397493Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer CellsAndrea M. Chambers0Kyle B. Lupo1Sandro Matosevic2Sandro Matosevic3Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United StatesDepartment of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United StatesDepartment of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United StatesCenter for Cancer Research, Purdue University, West Lafayette, IN, United StatesEnergy metabolism is key to the promotion of tumor growth, development, and metastasis. At the same time, cellular metabolism also mediates immune cell survival, proliferation and cytotoxic responses within the tumor microenvironment. The ability of natural killer cells to eradicate tumors relies on their ability to functionally persist for the duration of their anti-tumor effector activity. However, a tumor's altered metabolic requirements lead to compromised functional responses of cytokine-activated natural killer cells, which result in decreased effectiveness of adoptive cell-based immunotherapies. Tumors exert these immunosuppressive effects through a number of mechanisms, a key driver of which is hypoxia. Hypoxia also fuels the generation of adenosine from the cancer-associated ectoenzymes CD39 and CD73. Adenosine's immunosuppression manifests in decreased proliferation and impaired anti-tumor function, with adenosinergic signaling emerging as an immunometabolic checkpoint blockade target. Understanding such immunometabolic suppression is critical in directing the engineering of a new generation of natural killer cell-based immunotherapies that have the ability to more effectively target difficult-to-treat solid tumors.https://www.frontiersin.org/article/10.3389/fimmu.2018.02517/fullimmunometabolismnatural killer cellsimmunotherapytumor microenvironmentadenosine |
| spellingShingle | Andrea M. Chambers Kyle B. Lupo Sandro Matosevic Sandro Matosevic Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells Frontiers in Immunology immunometabolism natural killer cells immunotherapy tumor microenvironment adenosine |
| title | Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells |
| title_full | Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells |
| title_fullStr | Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells |
| title_full_unstemmed | Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells |
| title_short | Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells |
| title_sort | tumor microenvironment induced immunometabolic reprogramming of natural killer cells |
| topic | immunometabolism natural killer cells immunotherapy tumor microenvironment adenosine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02517/full |
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