Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion
Malignant pleural effusion (MPE) is a functional ‘cold’ tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detec...
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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.2022.2160558 |
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| author | Zi-Hao Wang Pei Zhang Wen-Bei Peng Lin-Lin Ye Xuan Xiang Xiao-Shan Wei Yi-Ran Niu Si-Yu Zhang Qian-Qian Xue Hao-Lei Wang Qiong Zhou |
| author_facet | Zi-Hao Wang Pei Zhang Wen-Bei Peng Lin-Lin Ye Xuan Xiang Xiao-Shan Wei Yi-Ran Niu Si-Yu Zhang Qian-Qian Xue Hao-Lei Wang Qiong Zhou |
| author_sort | Zi-Hao Wang |
| collection | DOAJ |
| description | Malignant pleural effusion (MPE) is a functional ‘cold’ tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3+ NKT-like cells. Similar to Treg cells, FOXP3+ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3+ NKT-like cells in human MPE. |
| format | Article |
| id | doaj-art-cdce253ca4ef4a50afc71bfe90a00a5f |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-cdce253ca4ef4a50afc71bfe90a00a5f2025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2022.2160558Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusionZi-Hao Wang0Pei Zhang1Wen-Bei Peng2Lin-Lin Ye3Xuan Xiang4Xiao-Shan Wei5Yi-Ran Niu6Si-Yu Zhang7Qian-Qian Xue8Hao-Lei Wang9Qiong Zhou10Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaMalignant pleural effusion (MPE) is a functional ‘cold’ tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3+ NKT-like cells. Similar to Treg cells, FOXP3+ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3+ NKT-like cells in human MPE.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2160558Malignant pleural effusionNKT-like cellFOXP3MCT1lactylationscRNA-seq |
| spellingShingle | Zi-Hao Wang Pei Zhang Wen-Bei Peng Lin-Lin Ye Xuan Xiang Xiao-Shan Wei Yi-Ran Niu Si-Yu Zhang Qian-Qian Xue Hao-Lei Wang Qiong Zhou Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion OncoImmunology Malignant pleural effusion NKT-like cell FOXP3 MCT1 lactylation scRNA-seq |
| title | Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion |
| title_full | Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion |
| title_fullStr | Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion |
| title_full_unstemmed | Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion |
| title_short | Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion |
| title_sort | altered phenotypic and metabolic characteristics of foxp3 cd3 cd56 natural killer t nkt like cells in human malignant pleural effusion |
| topic | Malignant pleural effusion NKT-like cell FOXP3 MCT1 lactylation scRNA-seq |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2160558 |
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