CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression
Infusion of natural killer (NK) cells is an attractive therapeutic modality in patients with cancer. However, the activity of NK cells is regulated by several mechanisms operating within solid tumors. Regulatory T (Treg) cells suppress NK cell activity through various mechanisms including deprivatio...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2175517 |
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| _version_ | 1850035429950095360 |
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| author | Ziqing Chen Le Tong Shi Yong Neo Shuijie Li Jiwei Gao Susanne Schlisio Andreas Lundqvist |
| author_facet | Ziqing Chen Le Tong Shi Yong Neo Shuijie Li Jiwei Gao Susanne Schlisio Andreas Lundqvist |
| author_sort | Ziqing Chen |
| collection | DOAJ |
| description | Infusion of natural killer (NK) cells is an attractive therapeutic modality in patients with cancer. However, the activity of NK cells is regulated by several mechanisms operating within solid tumors. Regulatory T (Treg) cells suppress NK cell activity through various mechanisms including deprivation of IL-2 via the IL-2 receptor alpha (CD25). Here, we investigate CD25 expression on NK cells to confer persistence in Treg cells containing solid tumor models of renal cell carcinoma (RCC). Compared with IL-2, stimulation with IL-15 increases the expression of CD25 resulting in enhanced response to IL-2 as evidenced by increased phosphorylation of STAT5. Compared with CD25dim NK cells, CD25bright NK cells isolated from IL-15 primed NK cells display increased proliferative and metabolic activity as well as increased ability to persist in Treg cells containing RCC tumor spheroids. These results support strategies to enrich for or selectively expand CD25bright NK cells for adoptive cellular therapy of NK cells. |
| format | Article |
| id | doaj-art-e02799ceb39a4ea993f8747d63d70183 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-e02799ceb39a4ea993f8747d63d701832025-08-20T02:57:29ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2175517CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppressionZiqing Chen0Le Tong1Shi Yong Neo2Shuijie Li3Jiwei Gao4Susanne Schlisio5Andreas Lundqvist6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenInfusion of natural killer (NK) cells is an attractive therapeutic modality in patients with cancer. However, the activity of NK cells is regulated by several mechanisms operating within solid tumors. Regulatory T (Treg) cells suppress NK cell activity through various mechanisms including deprivation of IL-2 via the IL-2 receptor alpha (CD25). Here, we investigate CD25 expression on NK cells to confer persistence in Treg cells containing solid tumor models of renal cell carcinoma (RCC). Compared with IL-2, stimulation with IL-15 increases the expression of CD25 resulting in enhanced response to IL-2 as evidenced by increased phosphorylation of STAT5. Compared with CD25dim NK cells, CD25bright NK cells isolated from IL-15 primed NK cells display increased proliferative and metabolic activity as well as increased ability to persist in Treg cells containing RCC tumor spheroids. These results support strategies to enrich for or selectively expand CD25bright NK cells for adoptive cellular therapy of NK cells.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2175517Natural killer cellsregulatory T cellsIL-15CD25tumor microenvironment |
| spellingShingle | Ziqing Chen Le Tong Shi Yong Neo Shuijie Li Jiwei Gao Susanne Schlisio Andreas Lundqvist CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression OncoImmunology Natural killer cells regulatory T cells IL-15 CD25 tumor microenvironment |
| title | CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression |
| title_full | CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression |
| title_fullStr | CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression |
| title_full_unstemmed | CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression |
| title_short | CD25bright NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression |
| title_sort | cd25bright nk cells display superior function and metabolic activity under regulatory t cell mediated suppression |
| topic | Natural killer cells regulatory T cells IL-15 CD25 tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2175517 |
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