{"title":"巨噬细胞和成纤维细胞之间的烟酰胺代谢对峙可操控胃癌的微环境","authors":"Yu Jiang, Yawen Wang, Guofeng Chen, Fei Sun, Qijing Wu, Qiong Huang, Dongqiang Zeng, Wenjun Qiu, Jiao Wang, Zhiqi Yao, Bishan Liang, Shaowei Li, Jianhua Wu, Na Huang, Yuanyuan Wang, Jingsong Chen, Xiaohui Zhai, Li Huang, Beibei Xu, Masami Yamamoto, Min Shi","doi":"10.1016/j.cmet.2024.05.013","DOIUrl":null,"url":null,"abstract":"<p>Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic “face-off” mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8<sup>+</sup> T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8<sup>+</sup> T cell cytotoxicity and the anti-PD-1 response in gastric cancer.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"111 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer\",\"authors\":\"Yu Jiang, Yawen Wang, Guofeng Chen, Fei Sun, Qijing Wu, Qiong Huang, Dongqiang Zeng, Wenjun Qiu, Jiao Wang, Zhiqi Yao, Bishan Liang, Shaowei Li, Jianhua Wu, Na Huang, Yuanyuan Wang, Jingsong Chen, Xiaohui Zhai, Li Huang, Beibei Xu, Masami Yamamoto, Min Shi\",\"doi\":\"10.1016/j.cmet.2024.05.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic “face-off” mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8<sup>+</sup> T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8<sup>+</sup> T cell cytotoxicity and the anti-PD-1 response in gastric cancer.</p>\",\"PeriodicalId\":9840,\"journal\":{\"name\":\"Cell metabolism\",\"volume\":\"111 1\",\"pages\":\"\"},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell metabolism\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmet.2024.05.013\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.05.013","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer
Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic “face-off” mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.