{"title":"Astrocyte TRAIL promotes GBM","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02189-5","DOIUrl":null,"url":null,"abstract":"<p>Glioblastoma (GBM) is an aggressive tumor with limited treatment options. In <i>Nature</i>, Faust Akl et al. show that both human and mouse GBM indirectly suppress adaptive immune antitumor responses by inducing TRAIL expression in astrocytes. TRAIL<sup>+</sup> astrocytes trigger CD4<sup>+</sup> and CD8<sup>+</sup> T cell apoptosis by cognate interaction with DR4 and DR5 death receptors expressed on their cell surface. In the tumor microenvironment, the tryptophan metabolite kynurenine induces expression of <i>IL11</i> in human GBM cells, which in turn activates STAT3-regulated expression of TRAIL (encoded by <i>TNFSF10</i>) in neighboring astrocytes. In mouse models of GBM, blockade of either IL-11 or TRAIL increased survival. Hence, this astrocyte-dependent IL-11–TRAIL axis might prove to be a potential therapy option for patients with GBM.</p><p><b>Original reference:</b> <i>Nature</i> https://doi.org/10.1038/s41586-025-08997-x (2025)</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"15 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-025-02189-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Glioblastoma (GBM) is an aggressive tumor with limited treatment options. In Nature, Faust Akl et al. show that both human and mouse GBM indirectly suppress adaptive immune antitumor responses by inducing TRAIL expression in astrocytes. TRAIL+ astrocytes trigger CD4+ and CD8+ T cell apoptosis by cognate interaction with DR4 and DR5 death receptors expressed on their cell surface. In the tumor microenvironment, the tryptophan metabolite kynurenine induces expression of IL11 in human GBM cells, which in turn activates STAT3-regulated expression of TRAIL (encoded by TNFSF10) in neighboring astrocytes. In mouse models of GBM, blockade of either IL-11 or TRAIL increased survival. Hence, this astrocyte-dependent IL-11–TRAIL axis might prove to be a potential therapy option for patients with GBM.
Original reference:Nature https://doi.org/10.1038/s41586-025-08997-x (2025)
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.
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