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
单细胞 CyTOF 鉴定肝内胆管癌中具有临床意义的 CD39⁺PD-1⁺CD8⁺ T 细胞与 CD39⁺ 调节性 T 细胞亚群
英文原题：Identification of clinically relevant subsets CD39(+)PD-1(+)CD8(+) T cells and CD39(+) regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.
查看英文原题
Identification of clinically relevant subsets CD39(+)PD-1(+)CD8(+) T cells and CD39(+) regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.
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中文摘要
肝内胆管癌（iCCA）是一种侵袭性肝脏恶性肿瘤，治疗选择有限且预后极差。肿瘤免疫微环境（TIME）对iCCA进展至关重要，但其整体特征尚未完全阐明。本研究采用飞行时间质谱流式技术（CyTOF），全面分析新鲜iCCA肿瘤样本及邻近癌旁肝组织中的免疫细胞群。值得注意的是，与癌旁肝组织相比，iCCA病灶中的NK细胞比例显著降低。相反，TIME内免疫抑制性CD39⁺Foxp3⁺CD4⁺调节性T细胞（CD39⁺ Treg）和耗竭样CD8⁺ T细胞（CD39和PD-1表达明显）富集，并在独立患者队列（n=140）中通过多重免疫荧光染色得到验证。关键的是，肿瘤浸润CD39⁺ Treg和CD39⁺PD-1⁺CD8⁺ T细胞是独立预后指标，均与iCCA不良预后相关。这些发现揭示了iCCA复杂的免疫图谱，为疾病管理和新型癌症免疫疗法提供了重要见解。
展开英文摘要原文
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete.
This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues.
Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39 + Foxp3 + CD4 + regulatory T cells (CD39 + T-regs) and exhausted-like CD8 + T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140).
Crucially, tumor-infiltrating CD39 + T-regs and CD39 + PD-1 + CD8 + T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA.
These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.
论文信息
- 作者
- Zhang QW、Zhu MX、Liu WF、Rui WW、Chen Y、Ding XY、Jiang YS、Wu ZY
- 第一作者单位
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.China
- 通讯作者单位
- Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Electronic address: liu.binbin@zs-hospital.sh.cn.China
- 期刊
- Translational oncology2024 Jun
- 原文标识
- PubMed 38608405 · DOI 10.1016/j.tranon.2024.101954
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