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:Deciphering the role of KLRB1: a novel prognostic indicator in hepatocellular carcinoma.
Deciphering the role of KLRB1: a novel prognostic indicator in hepatocellular carcinoma.
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KLRB1 在 HCC 中成为一个有前景的生物标志物,其在外周血 NK 和 T 细胞上的下调提示潜在的预后价值。进一步阐明 KLRB1 在 HCC 中的作用可能为靶向免疫疗法的开发和患者预后的改善铺平道路。
肝细胞癌(HCC)是全球重大的健康挑战,发病率和死亡率均较高。T细胞和自然杀伤(NK)细胞在此背景下发挥关键作用,然而HCC能够逃避免疫监视。CD161(KLRB1)是一种C型凝集素受体,可调节免疫反应,表达于NK细胞和一部分T细胞上。其在HCC中的相关性仍知之甚少,关于其对患者预后影响的发现存在矛盾。
利用TCGA数据和单细胞分析,我们研究了KLRB1在HCC中的生物学功能。收集了126例HCC患者的外周血样本,以评估NK细胞和T细胞上KLRB1的表达。使用受试者工作特征曲线(ROC)分析评估了KLRB1在NK细胞和CD8 + T细胞上的诊断性能,同时使用Kaplan-Meier分析和COX回归模型评估了其预后意义。
TCGA数据分析显示,KLRB1表达与免疫激活,尤其是T细胞激活,存在显著相关性。单细胞数据进一步表明,在HCC中,组织驻留NK和T细胞中KLRB1表达升高,这些细胞共表达免疫激活标志物。临床数据显示,与健康个体相比,HCC患者NK和T细胞上KLRB1表达下调,且表达水平较低与较差预后相关。
Hepatocellular carcinoma (HCC) represents a significant global health challenge with high incidence and mortality rates. T cells and natural killer (NK) cells are pivotal in this context, yet HCC can evade immune surveillance. CD161 (KLRB1), a C-type lectin receptor, modulates immune responses and is expressed on NK cells and a subset of T cells. Its relevance in HCC remains poorly understood, with conflicting findings regarding its impact on patient prognosis.
Utilizing TCGA data and single-cell analysis, we investigated the biological functions of KLRB1 in HCC. Peripheral blood samples from 126 HCC patients were collected to assess KLRB1 expression on NK and T cells. The diagnostic performance of KLRB1 on NK and CD8 + T cells was evaluated using receiver operating characteristic curve (ROC) analysis, while its prognostic significance was assessed using Kaplan-Meier analysis and COX regression models.
Analysis of TCGA data revealed a significant correlation between KLRB1 expression and immune activation, particularly T cell activation. Single-cell data further demonstrated elevated KLRB1 expression in tissue-resident NK and T cells within HCC, which co-expressed markers of immune activation. Clinical data showed downregulated KLRB1 expression on NK and T cells in HCC patients compared to health individuals, with lower expression levels correlating with poorer prognosis.
KLRB1 emerges as a promising biomarker in HCC, with its downregulation on peripheral blood NK and T cells suggesting potential prognostic value. Further elucidation of KLRB1's role in HCC may pave the way for the development of targeted immunotherapies and the improvement of patient outcomes.
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