Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng
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引用次数: 0
摘要
作为肿瘤免疫微环境(TIME)的重要组成部分,常住微生物群促进了多种癌症类型的肿瘤发生。在这里,我们整合了多种类型的全息数据,包括微生物组、转录组和代谢组数据,以研究胃癌(GC)中瘤内细菌的功能作用。微生物组被用来将胃癌样本分为六个亚型,链球菌或假单胞菌含量高的患者预后明显较差。进一步的检测发现,副链球菌(SA)能促进肿瘤细胞的增殖和转移,同时抑制 CD8+ T 细胞的分化和浸润。然而,抗生素治疗可明显抑制 SA+ 小鼠体内的肿瘤发生。我们进一步证实,SA 精氨酸通路增加了鸟氨酸的丰度,而鸟氨酸可能是重塑 TIME 的主要因素。我们的研究结果表明,SA作为一种新的危险因素,在GC的发生和发展过程中起着重要作用,这表明SA可能是诊断和治疗GC的一个有前途的靶点。
Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression.
As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8+ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA+ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.
Cell DiscoveryBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍:
Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research.
Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals.
In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.