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
循环 NK 细胞上免疫检查点 TIM-3、LAG-3、TIGIT 和 Siglec-7 的差异表达——健康供者与胃癌患者的对比研究见解
英文原题：Differential Expression of Immune Checkpoints TIM-3, LAG-3, TIGIT, and Siglec-7 on Circulating Natural Killer Cells - Insights from Healthy Donors Compared to Gastric Cancer Patients.
查看英文原题
Differential Expression of Immune Checkpoints TIM-3, LAG-3, TIGIT, and Siglec-7 on Circulating Natural Killer Cells - Insights from Healthy Donors Compared to Gastric Cancer Patients.
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研究概要
我们的发现提示 LAG-3 作为下一代检查点分子的潜力，与 Siglec-7 并列。特别是靶向唾液酸-Siglec-7 轴可能在未来为多种癌症类型提供有前景的治疗策略。
研究思路结论见上方概要
方法
为了研究这一困境，我们通过NK细胞与K562细胞共孵育模拟体外激活，并分析了TIM-3、LAG-3、TIGIT和Siglec-7的表达。之后，我们使用流式细胞术分析了35名健康供者循环NK细胞的检查点表达，并将其与胃癌患者（n = 21）中的表达进行了比较。
结果
在健康供者中，我们观察到25-97%的循环NK细胞表达TIM-3、TIGIT和Siglec-7，而仅有一小部分0.6%表达LAG-3。将健康供者的外周血单个核细胞与K562细胞共孵育导致NK细胞上TIM-3和TIGIT的表达水平升高。相反，胃癌患者的NK细胞显示LAG-3表达增加和Siglec-7表达减少。
展开英文摘要原文
METHODS
To investigate this dilemma, we simulated in vitro activation by NK-cell co-incubation with K562 cells and analyzed expression of TIM-3, LAG-3, TIGIT, and Siglec-7. After that, we analyzed the checkpoint expression of circulating NK cells from 35 healthy donors and compared it to their expression in patients with gastric cancer (n = 21) using flow cytometry.
RESULTS
In healthy donors, we observed that 25-97% of all circulating NK cells expressed TIM-3, TIGIT and Siglec-7, while only a small fraction of 0.6% expressed LAG-3. Co-incubation of peripheral blood mononuclear cells from healthy donors with K562 cells resulted in heightened expression levels of TIM-3 and TIGIT on NK cells. Conversely, NK cells in patients with gastric cancer showed an increased LAG-3 and reduced Siglec-7 expression.
CONCLUSION
Our findings suggest the potential of LAG-3 as a next-generation checkpoint molecule, alongside Siglec-7. Especially targeting the sialic acid-Siglec-7 axis may offer promising therapeutic strategies for various cancer types in the future. </p>.
论文信息
- 作者
- Seiffert S、Seiffert S、Blaudszun AR、Shibru B、Körfer J、Köhl U、Fricke S、Sack U
- 通讯作者单位
- Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany.Germany
- 文献类型
- 对照研究
- 期刊
- Oncology research and treatment2025
- 原文标识
- PubMed 40179832 · DOI 10.1159/000545429
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