{"title":"GPR34 是 ILC1 介导的抗肿瘤免疫的代谢免疫检查点","authors":"Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou","doi":"10.1038/s41590-024-01973-z","DOIUrl":null,"url":null,"abstract":"Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we found that G-protein-coupled receptor 34 (GPR34), a receptor for lysophosphatidylserine (LysoPS), was highly expressed on ILC1s but not on conventional natural killer cells in the tumor microenvironment. LysoPS was enriched in the tumor microenvironment and could inhibit ILC1 activation via GPR34. Genetic deletion of LysoPS synthase Abhd16a expression in tumors or Gpr34 expression in ILC1s or antagonizing GPR34 enhanced ILC1 antitumor activity. In individuals with cancer, ABHD16A expression in tumors or GPR34 expression in ILC1s was inversely correlated with the antitumor activity of ILC1s or ILC1-like cells. Thus, our results demonstrate that manipulating ILC1s can induce potent antitumor immunity, and GPR34 is a metabolic immune checkpoint that can be targeted to develop ILC1-based immunotherapy. Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2057-2067"},"PeriodicalIF":27.7000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity\",\"authors\":\"Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou\",\"doi\":\"10.1038/s41590-024-01973-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we found that G-protein-coupled receptor 34 (GPR34), a receptor for lysophosphatidylserine (LysoPS), was highly expressed on ILC1s but not on conventional natural killer cells in the tumor microenvironment. LysoPS was enriched in the tumor microenvironment and could inhibit ILC1 activation via GPR34. Genetic deletion of LysoPS synthase Abhd16a expression in tumors or Gpr34 expression in ILC1s or antagonizing GPR34 enhanced ILC1 antitumor activity. In individuals with cancer, ABHD16A expression in tumors or GPR34 expression in ILC1s was inversely correlated with the antitumor activity of ILC1s or ILC1-like cells. Thus, our results demonstrate that manipulating ILC1s can induce potent antitumor immunity, and GPR34 is a metabolic immune checkpoint that can be targeted to develop ILC1-based immunotherapy. Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\"25 11\",\"pages\":\"2057-2067\"},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2024-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41590-024-01973-z\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41590-024-01973-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity
Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we found that G-protein-coupled receptor 34 (GPR34), a receptor for lysophosphatidylserine (LysoPS), was highly expressed on ILC1s but not on conventional natural killer cells in the tumor microenvironment. LysoPS was enriched in the tumor microenvironment and could inhibit ILC1 activation via GPR34. Genetic deletion of LysoPS synthase Abhd16a expression in tumors or Gpr34 expression in ILC1s or antagonizing GPR34 enhanced ILC1 antitumor activity. In individuals with cancer, ABHD16A expression in tumors or GPR34 expression in ILC1s was inversely correlated with the antitumor activity of ILC1s or ILC1-like cells. Thus, our results demonstrate that manipulating ILC1s can induce potent antitumor immunity, and GPR34 is a metabolic immune checkpoint that can be targeted to develop ILC1-based immunotherapy. Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.