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:Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer.
Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer.
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HLA-E 可作为 GC 根治性切除术后的预后因素,HLA-E 表达联合 NK 状态可作为晚期 GC 的敏感预后生物标志物。
NKG2A/HLA-E通路作为一种免疫检查点,具有使用治疗性抗体进行抑制的潜力。通过该通路,免疫细胞失去活性,从而使癌症得以进展。我们旨在确定HLA-E表达联合NK细胞状态是否可作为胃癌(GC)的预后生物标志物。
我们纳入了接受根治性胃切除术的晚期GC患者(n = 232)。进行了HLA-E总体表达以及CD56和CD3表达以识别NK细胞的免疫组化分析。进行生存分析以评估HLA-E表达和NK状态的意义。
HLA-E阳性患者为104例(41.3%),与HLA-E阴性患者相比,其无复发生存期(RFS)预后显著更差。此外,NK低状态患者的RFS预后较NK高状态患者更差。RFS的统计分析表明,HLA-E表达是预后不良的显著独立因素(HR 1.57,95% CI 1.04-2.36,P = 0.031)。此外,HLA-E阳性且NK低状态的患者RFS最短,尤其是上GC组患者。
The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC).
We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy. Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status.
Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04-2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group.
HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.
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