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
英文原题:Different endurance exercises modulate NK cell cytotoxic and inhibiting receptors.
Different endurance exercises modulate NK cell cytotoxic and inhibiting receptors.
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急性和慢性耐力训练均可能通过 AhR/IDO 轴调节 NK 细胞功能。
IDO的诱导依赖于AhR激活并形成AhR/IDO轴。活化的AhR可转录多种靶基因,包括NK细胞的细胞毒性受体和抑制性受体。我们研究急性运动和不同长期耐力训练方案是否会影响AhR、IDO水平以及NK细胞激活受体NKG2D和抑制受体KIR2DL1。
TOP研究(NCT02883699)中21例成年乳腺癌和前列腺癌患者,在心肺运动试验(CPET)后随机接受为期12周的(1)常规耐力训练或(2)极化耐力训练。于CPET前、CPET后即刻、CPET后1小时及12周干预后采集血清。将自体血清与NK-92细胞孵育后,采用流式细胞术分析AhR、IDO、KIR2DL1和NKG2D。急性效应采用方差分析,慢性效应采用协方差分析。
急性运动:IDO水平随时间变化,CPET后至1小时后显著升高(p=0.03)。KIR2DL1水平随时间显著下降(p<0.01)。NKG2D水平保持稳定(p=0.31)。慢性运动:IDO和NKG2D均观察到显著的组别×时间交互作用、显著时间效应,以及干预12周后的显著差异(IDO:均p<0.01;NKG2D:均p>0.05)。
急性和慢性耐力训练都可能通过AhR/IDO轴调节NK细胞功能。运动可能是免疫调节的重要因素,这一发现具有临床意义。
Induction of IDO depends on the activation of AhR forming the AhR/IDO axis. Activated AhR can transcribe various target genes including cytotoxic and inhibiting receptors of NK cells. We investigated whether AhR and IDO levels as well as activating (NKG2D) and inhibiting (KIR2DL1) NK cell receptors are influenced by acute exercise and different chronic endurance exercise programs.
21 adult breast and prostate cancer patients of the TOP study (NCT02883699) were randomized to intervention programs of 12 weeks of (1) endurance standard training or (2) endurance polarized training after a cardiopulmonary exercise test (CPET). Serum was collected pre-CPET, immediately post-CPET, 1 h post-CPET and after 12 weeks post-intervention. Flow cytometry analysis was performed on autologous serum incubated NK-92 cells for: AhR, IDO, KIR2DL1 and NKG2D. Differences were investigated using analysis-of-variance for acute and analysis-of-covariance for chronic effects.
Acute exercise: IDO levels changed over time with a significant increase from post-CPET to 1 h post-CPET (p = 0.03). KIR2DL1 levels significantly decreased over time (p < 0.01). NKG2D levels remained constant (p = 0.31). Chronic exercise: for both IDO and NKG2D a significant group time interaction, a significant time effect and a significant difference after 12 weeks of intervention were observed (IDO: all p < 0.01, NKG2D: all p > 0.05).
Both acute and chronic endurance training may regulate NK cell function via the AhR/IDO axis. This is clinically relevant, as exercise emerges to be a key player in immune regulation.
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