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Leucine-tRNA-synthase-2-expressing B cells contribute to colorectal cancer immunoevasion.
Wang, Zhiqiang; Lu, Zhou; Lin, Shengli; Xia, Jie; Zhong, Ziwen; Xie, Zhangjuan; Xing, Yun; Qie, Jingbo; Jiao, Mengxia; Li, Yifan; Wen, Haoyu; Zhao, Pengyuan; Zhang, Dan; Zhou, Pinghong; Qian, Jiawen; Luo, Feifei; Wang, Luman; Yu, Hongxiu; Liu, Jie; Gu, Jie; Liu, Ronghua; Chu, Yiwei.
Affiliation
  • Wang Z; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Lu Z; Liver Cancer Institute, Department of Anesthesiology, Zhongshan Hospital, Shanghai 200032, China.
  • Lin S; Endoscopy Center, Endoscopy Research Institute, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • Xia J; Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Zhong Z; Liver Cancer Institute, Department of Anesthesiology, Zhongshan Hospital, Shanghai 200032, China.
  • Xie Z; Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Xing Y; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Qie J; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Jiao M; Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Li Y; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Wen H; Endoscopy Center, Endoscopy Research Institute, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • Zhao P; Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Zhang D; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Zhou P; Endoscopy Center, Endoscopy Research Institute, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • Qian J; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Luo F; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China.
  • Wang L; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Yu H; Institutes of Biomedical Sciences, Shanghai Stomatological Hospital, Fudan University, Shanghai 200032, China.
  • Liu J; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China.
  • Gu J; Endoscopy Center, Endoscopy Research Institute, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • Liu R; Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: ronghualiu@fudan.edu.cn.
  • Chu Y; Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yiweichu@fudan.edu.cn.
Immunity ; 55(6): 1067-1081.e8, 2022 06 14.
Article in En | MEDLINE | ID: mdl-35659337
ABSTRACT
Immunoregulatory B cells impede antitumor immunity through unknown features and mechanisms. We report the existence of leucine-tRNA-synthase-2 (LARS2)-expressing B cell (LARS B) subset with a transforming growth factor-ß1 (TGF-ß1)-dominant regulatory feature in both mouse and human progressive colorectal cancer (CRC). Of note, LARS B cells exhibited a leucine nutrient preference and displayed active mitochondrial aminoacyl-tRNA biosynthesis. They were located outside the tertiary lymphoid structure and correlated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet induced LARS B cell generation, whereas LARS B cell deletion by Lars2 gene ablation or leucine blockage repressed CRC immunoevasion. Mechanistically, LARS2 programmed mitochondrial nicotinamide adenine dinucleotide (NAD+) regeneration and oxidative metabolism, thus determining the regulatory feature of LARS B cells in which the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) was involved. We propose a leucine-dieting scheme to inhibit LARS B cells, which is safe and useful for CRC therapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Amino Acyl-tRNA Synthetases Limits: Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2022 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Amino Acyl-tRNA Synthetases Limits: Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2022 Type: Article Affiliation country: China