RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一种来自健康人体微生物群成员的荚膜多糖激活 Lag-3-NK 细胞轴以抑制结肠癌并增强免疫治疗
英文原题：A capsular polysaccharide from a healthy human microbiota member activates a Lag-3-NK cell axis to restrain colon cancer and augment immunotherapy.
查看英文原题
A capsular polysaccharide from a healthy human microbiota member activates a Lag-3-NK cell axis to restrain colon cancer and augment immunotherapy.
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中文摘要
结直肠癌（CRC）在全球范围内日益增加，因此有必要寻找预防措施。将 CRC 患者和非 CRC 个体的微生物群移植至小鼠的研究显示，未患病个体携带可减少肿瘤形成的微生物，并提示 Bacteroides uniformis 具有保护作用。CRC 患者体内 B. uniformis 减少；在小鼠中预先给予 B. uniformis 可减缓肿瘤生长。B. uniformis 介导的保护作用依赖 NK 细胞，而不依赖 T 细胞。CRC 对免疫疗法应答欠佳，但加入 B. uniformis 可通过依赖 NK 细胞的机制恢复对抗 CTLA-4 治疗的应答。研究还报告，LAG-3 高表达与 CRC 患者生存较好相关，且 B. uniformis 介导的保护作用依赖先天免疫细胞中的 LAG-3。NK 细胞活性诱导和肿瘤生长减少依赖 B. uniformis 的特定荚膜多糖。
因此，健康个体携带可抑制肿瘤、预防癌症发生的微生物，并有望将其用于治疗。
展开英文摘要原文
Colorectal cancer (CRC) is increasing globally, making identification of preventative measures necessary. Transplantation of the microbiota from CRC and non-CRC patients into mice demonstrates that non-diseased individuals possess organisms that reduce tumor formation and highlights Bacteriodes uniformis as protective. B.
uniformis is reduced in humans with CRC, and proactive treatment with B. uniformis slows tumor growth in mice. Natural killer (NK) cells, but not T cells, are required for B. uniformis-mediated protection. CRC is recalcitrant to immunotherapies; however, addition of B. uniformis restores response to -CTLA-4 treatment in an NK cell-dependent manner.
We report that high Lag-3 expression is associated with greater survival in CRC patients and that B. uniformis-mediated protection is reliant on Lag-3 in innate cells. Induction of NK cell activity and reduced tumor growth is dependent on a specific B. uniformis capsular polysaccharide.
Thus, healthy individuals possess tumor suppressor microbes that prevent cancer development and can be harnessed therapeutically.
论文信息
- 作者
- Weis AM、Bauer KM、Tang WW、Stephen-Victor E、Bell R、Brown DG、Ekiz HA、Tran V
- 第一作者单位
- Division of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.United States
- 通讯作者单位
- Division of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: june.round@path.utah.edu.United States
- 期刊
- Cell reports2025 Sep 23
- 原文标识
- PubMed 40849910 · DOI 10.1016/j.celrep.2025.116172
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