Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells
The exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associate...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460281 |
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| author | Meng Li Di Li Hai-Yun Wang Weixin Zhang Zhenjian Zhuo Huiqin Guo Jiabin Liu Yue Zhuo Jue Tang Jing He Lei Miao |
| author_facet | Meng Li Di Li Hai-Yun Wang Weixin Zhang Zhenjian Zhuo Huiqin Guo Jiabin Liu Yue Zhuo Jue Tang Jing He Lei Miao |
| author_sort | Meng Li |
| collection | DOAJ |
| description | The exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associated with leptin expression in advanced NB. Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg cells instead of Th17 cells, which benefited from NB cell proliferation, migration, and drug resistance. Mechanically, leptin in NB cells blunted the activity of carnitine palmitoyltransferase 2 (CPT2), the key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, which depresses oxidative phosphorylation (OXPHOS) for energy supply and increases lactic acid (LA) production from glycolysis to modulate CD4+ T cell differentiation. These findings highlight that excess leptin contributes to lipid metabolism dysfunction in NB cells and subsequently misdirects CD4+ T cell differentiation in tumor micro-environment (TME), indicating that targeting leptin could be a therapeutic strategy for retarding NB progression. |
| format | Article |
| id | doaj-art-b3c6d18abb1b4a22ab4af8b3ca91ae8a |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-b3c6d18abb1b4a22ab4af8b3ca91ae8a2025-02-04T13:30:18ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2460281Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cellsMeng Li0Di Li1Hai-Yun Wang2Weixin Zhang3Zhenjian Zhuo4Huiqin Guo5Jiabin Liu6Yue Zhuo7Jue Tang8Jing He9Lei Miao10Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaDepartment of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaLaboratory Animal Center, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, ChinaThe exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associated with leptin expression in advanced NB. Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg cells instead of Th17 cells, which benefited from NB cell proliferation, migration, and drug resistance. Mechanically, leptin in NB cells blunted the activity of carnitine palmitoyltransferase 2 (CPT2), the key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, which depresses oxidative phosphorylation (OXPHOS) for energy supply and increases lactic acid (LA) production from glycolysis to modulate CD4+ T cell differentiation. These findings highlight that excess leptin contributes to lipid metabolism dysfunction in NB cells and subsequently misdirects CD4+ T cell differentiation in tumor micro-environment (TME), indicating that targeting leptin could be a therapeutic strategy for retarding NB progression.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460281Neuroblastomalong-chain fatty acidleptinT cell differentiationtumor microenvironment |
| spellingShingle | Meng Li Di Li Hai-Yun Wang Weixin Zhang Zhenjian Zhuo Huiqin Guo Jiabin Liu Yue Zhuo Jue Tang Jing He Lei Miao Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells OncoImmunology Neuroblastoma long-chain fatty acid leptin T cell differentiation tumor microenvironment |
| title | Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells |
| title_full | Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells |
| title_fullStr | Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells |
| title_full_unstemmed | Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells |
| title_short | Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells |
| title_sort | leptin decreases th17 treg ratio to facilitate neuroblastoma via inhibiting long chain fatty acid catabolism in tumor cells |
| topic | Neuroblastoma long-chain fatty acid leptin T cell differentiation tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460281 |
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