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
HLA-G 和杀伤细胞免疫球蛋白样受体的表达在结直肠癌中会发生变化吗？
英文原题：Do the expressions of HLA-G and killer cell immunoglobulin-like receptors change in colorectal cancer?
查看英文原题
Do the expressions of HLA-G and killer cell immunoglobulin-like receptors change in colorectal cancer?
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研究概要
本研究强调了 CRC 患者中 HLA-G 和 KIR 标志物的表达增加，提示它们作为预后和预测标志物的潜力。我们的发现还表明，HLA-G 和 KIR 分子可能成为未来癌症免疫治疗策略中有价值的治疗靶点。
研究思路结论见上方概要
背景
免疫系统作为协调良好的防御机制，保护宿主免受外部病原体和内部威胁。癌细胞常表达免疫系统可识别为异己的表面抗原，可能触发免疫反应。然而，许多癌细胞通过下调或完全丢失这些表面抗原来逃避免疫检测。免疫系统依赖表面抗原和人类白细胞抗原（HLA）的表达来识别和靶向肿瘤细胞。肿瘤细胞逃避自然杀伤（NK）细胞的一种关键机制涉及HLA抗原的改变。已知结直肠癌（CRC）会引起免疫系统的多种变化，包括细胞表面HLA抗原表达增加、NK细胞功能降低以及免疫逃逸机制。本研究旨在通过检查肿瘤组织样本，探讨先天免疫及相关HLA-G分子在CRC发生中的可能作用。
方法
我们通过ELISA评估了可溶性HLA-G（sHLA-G）水平，通过免疫组化（IHC）研究了肿瘤样本中HLA-G表达的缺失，并评估了肿瘤组织中NK细胞上杀伤细胞免疫球蛋白样受体（KIR）的表达。
结果
HLA-G与sHLA-G水平之间未发现显著相关性（p = 0.641）。在患者样本中，16.7%（36例中的6例）HLA-G呈阳性，强度不一，而对照样本中未观察到染色。与对照样本相比，IHC染色显示CRC组织样本中KIR阳性率显著更高。我们研究的一个显著发现是同一肿瘤内KIR染色强度的变异性。我们不仅观察到肿瘤之间KIR表达的差异，还观察到同一肿瘤不同区域内的差异。此外，发现KIR表达与年龄之间存在显著关系。
展开英文摘要原文
MATERIALS AND METHODS
We evaluated soluble HLA-G (sHLA-G) levels via ELISA, investigated HLA-G expression loss in tumor samples through immunohistochemistry (IHC), and assessed killer cell immunoglobulin-like receptor (KIR) expression on NK cells in tumor tissues.
RESULTS
No significant correlation was found between HLA-G and sHLA-G levels (p = 0.641). Among patient samples, 16.7% (6 of 36) were positive for HLA-G, with varying intensities, while no staining was observed in control samples. Compared to control samples, IHC staining revealed a significantly higher rate of KIR positivity in CRC tissue samples. One notable finding of our study was the variability in KIR staining intensity within the same tumor. We observed differences in KIR expression not only between tumors, but also within distinct areas of the same tumor. Additionally, a significant relationship was found between KIR expression and age.
CONCLUSION
In conclusion, this study highlights the increased expression of both HLA-G and KIR markers in CRC patients, suggesting their potential as prognostic and predictive markers. Our findings also suggest that HLA-G and KIR molecules could represent valuable therapeutic targets for future cancer immunotherapy strategies.
论文信息
- 作者
- Dinçer E、Kaya Dağistanli F、Peker KD、Sakiz D、Abatay Sel F、Kivanç D、Şentürk Çiftçi H、Kekik Çinar Ç
- 第一作者单位
- Institute of Graduate Studies in Health Science, İstanbul University, İstanbul, Turkiye.Turkey
- 通讯作者单位
- Department of Medical Biology, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkiye.Turkey
- 期刊
- Turkish journal of medical sciences2025
- 原文标识
- PubMed 41234446 · DOI 10.55730/1300-0144.6073
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