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:Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma.
Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma.
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本研究揭示了 NK 细胞在 HNSC 中的重要性及其作为预后生物标志物的潜力。CFKZ 评分提供了一种有前景的方法,用于预测 HNSC 患者结局并指导个性化治疗决策。这些发现有助于我们理解 HNSC 免疫生物学,并对 HNSC 管理中的精准医学具有重要意义。
头颈部鳞状细胞癌(HNSC)是一种具有重要临床意义的难治性癌症。自然杀伤(NK)细胞已成为肿瘤免疫监视中的重要参与者,但其在HNSC中的作用及作为预后生物标志物的潜力仍不明确。
使用多种算法进行的定量分析确定,FCRL1、KIR3DL2和ZNF541是与局部NK细胞浸润及患者生存显著相关的分子。基于这些分子的预后模型展现出稳健的预测性能。
对高风险和低风险患者组的分析揭示了肿瘤微环境的显著差异,表明高风险患者存在抑制性免疫微环境。值得注意的是,低风险患者表现出对免疫治疗的潜在敏感性,并对axitinib、methotrexate、rapamycin和vorinostat等特定药物显示出良好反应。NK细胞作为先天免疫应答的重要效应细胞,被发现其在HNSC免疫中发挥关键作用。本研究为FCRL1、KIR3DL2、ZNF541与NK细胞浸润之间的相关性提供了有价值的见解,为未来研究它们在HNSC中的作用奠定了基础。高风险患者中NOTCH信号、MYC靶点、DNA修复、E2F靶点、上皮-间质转化、G2M检查点和有丝分裂纺锤体通路的激活,提示它们参与疾病进展和不良预后。
Head and neck squamous cell carcinoma (HNSC) is a challenging cancer with significant clinical implications. Natural killer (NK) cells have emerged as important players in tumor immunosurveillance, yet their role and potential as prognostic biomarkers in HNSC remain unclear.
Quantitative analysis using multiple algorithms identified FCRL1, KIR3DL2 and ZNF541 as molecules significantly associated with local NK cell infiltration and patient survival. A prognostic model based on these molecules demonstrated robust predictive performance.
Analysis of high- and low-risk patient groups revealed distinct differences in the tumor microenvironment, indicating an inhibitory immune microenvironment in high-risk patients. Notably, low-risk patients exhibited potential sensitivity to immunotherapy and showed favorable responses to specific drugs such as axitinib, methotrexate, rapamycin and vorinostat. NK cells, important effectors of the innate immune response, were found to play a crucial role in HNSC immunity. The present study provides valuable insights into the correlation between FCRL1, KIR3DL2, ZNF541 and NK cell infiltration, paving the way for future investigations into their roles in HNSC. Activation of NOTCH signaling, MYC targets, DNA repair, E2F targets, epithelial-mesenchymal transition, G2M checkpoint and mitotic spindle pathways in high-risk patients suggests their involvement in disease progression and poor prognosis.
The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.
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