{"title":"Alistipes finegoldii augments the efficacy of immunotherapy against solid tumors","authors":"Zhi-Ying Wu, Qi-Wen Wu, Yi Han, Shu-Jing Xiang, Ying-Nan Wang, Wen-Wei Wu, Yan-Xing Chen, Zi-Qing Feng, Yi-Yu Wang, Ze-Gong Xu, Huan-Chun He, Jun-Jie He, Jia-Qi Chen, Hui Sheng, Qi-Hua Zhang, Zi-Xian Wang, Kun Liao, Qi Zhao, Wei-Jian Mei, Pei-Rong Ding, Rui-Hua Xu","doi":"10.1016/j.ccell.2025.07.002","DOIUrl":null,"url":null,"abstract":"The emergence of immunotherapy has revolutionized cancer therapy. However, immunotherapeutic resistance remains a major obstacle for broader clinical application. Recent studies highlight that gut microbiota enhances immunotherapy by modulating anti-tumor immunity. In our investigation, we identify that <em>Alistipes finegoldii</em> (<em>A. finegoldii</em>) is associated with superior immunotherapy efficacy across multiple cohorts. Subsequent <em>in vitro</em> and <em>in vivo</em> experiments reveal that <em>A. finegoldii</em> enhances CD8<sup>+</sup> T cell chemotaxis via the CXCL16-CXCR6 axis, enhancing immunotherapy efficacy. Mechanistically, a lipoprotein derived from <em>A. finegoldii</em> (LIPOAF) activates the nuclear factor kappa B (NF-κB) signaling pathway to augment CXCL16 expression in CCR7<sup>+</sup> conventional dendritic cells through binding with the Toll-like receptor 2. Released CXCL16 subsequently facilitates the recruitment of CXCR6<sup>+</sup>CD8<sup>+</sup> T cells into the tumor microenvironment, effectively curbing tumor growth. Our findings suggest a promising strategy for treating solid tumors by combining <em>A. finegoldii</em> with immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"34 1","pages":""},"PeriodicalIF":44.5000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.07.002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The emergence of immunotherapy has revolutionized cancer therapy. However, immunotherapeutic resistance remains a major obstacle for broader clinical application. Recent studies highlight that gut microbiota enhances immunotherapy by modulating anti-tumor immunity. In our investigation, we identify that Alistipes finegoldii (A. finegoldii) is associated with superior immunotherapy efficacy across multiple cohorts. Subsequent in vitro and in vivo experiments reveal that A. finegoldii enhances CD8+ T cell chemotaxis via the CXCL16-CXCR6 axis, enhancing immunotherapy efficacy. Mechanistically, a lipoprotein derived from A. finegoldii (LIPOAF) activates the nuclear factor kappa B (NF-κB) signaling pathway to augment CXCL16 expression in CCR7+ conventional dendritic cells through binding with the Toll-like receptor 2. Released CXCL16 subsequently facilitates the recruitment of CXCR6+CD8+ T cells into the tumor microenvironment, effectively curbing tumor growth. Our findings suggest a promising strategy for treating solid tumors by combining A. finegoldii with immunotherapy.
期刊介绍:
Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows:
Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers.
Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice.
Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers.
Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies.
Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.