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
组蛋白乳酸化衍生的 TET2 增强 Arg1 介导的 MDSC 免疫抑制
英文原题：Histone lactylation-derived TET2 enhanced Arg1-mediated MDSC immunosuppression.
查看英文原题
Histone lactylation-derived TET2 enhanced Arg1-mediated MDSC immunosuppression.
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研究概要
本研究表明，组蛋白乳酸化介导的 TET2 改变为癌症治疗提供了一个新的治疗靶点。
研究思路结论见上方概要
方法
本研究利用Lewis肺癌细胞系建立肺癌异种移植模型；从小鼠脾脏中分离MDSCs用于后续实验。通过Western blotting分析蛋白表达，通过qRT-PCR分析mRNA表达，通过ChIP-qPCR分析蛋白质-DNA相互作用，通过MSP-qPCR分析DNA甲基化。
结果
本研究表明，组蛋白乳酸化增强MDSC的免疫抑制功能。在机制上，乳酸诱导的组蛋白乳酸化上调TET2，TET2以STAT3为桥梁，调控ARG1启动子甲基化以上调其表达，最终增强MDSC的免疫抑制功能。
展开英文摘要原文
METHODS
This study used the Lewis lung carcinoma cell line to establish a lung cancer xenograft model; MDSCs were isolated from the spleens of these mice for subsequent experiments. Protein expression was analyzed by Western blotting, mRNA expression by qRT-PCR, protein-DNA interactions by ChIP-qPCR, and DNA methylation by MSP-qPCR. RESULT: This research shows that histone lactylation enhances the immunosuppressive function of MDSCs. Mechanistically, lactate-induced histone lactylation upregulates TET2, which, using STAT3 as a bridge, modulates ARG1 promoter methylation to upregulate its expression and ultimately enhance the immunosuppressive function of MDSCs.
CONCLUSION
This research reveals that the histone lactylation-mediated alteration of TET2 presents a novel therapeutic target for cancer treatment.
论文信息
- 作者
- Da W、Dai Y、Shen B、Zhang Y、Bao P、Zhu W、Wang D、Wang S
- 单位
- Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.China
- 期刊
- Frontiers in immunology2025
- 原文标识
- PubMed 41624845 · DOI 10.3389/fimmu.2025.1677780
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