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:The alterations in peripheral lymphocyte subsets predict the efficacy and prognosis of immune checkpoint inhibitors in hepatocellular carcinoma.
The alterations in peripheral lymphocyte subsets predict the efficacy and prognosis of immune checkpoint inhibitors in hepatocellular carcinoma.
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免疫检查点抑制剂(ICI)治疗是肝细胞癌(HCC)患者有前景的疗法。然而,并非所有HCC患者都能从免疫治疗中获益。因此,迫切需要探索肝癌免疫治疗临床疗效和预后的标志物。本研究旨在探讨免疫治疗后外周血淋巴细胞亚群的变化,并评估其预测和预后价值。
纳入61例晚期HCC患者。在ICI治疗前后收集HCC患者的外周血样本,并通过流式细胞术检测淋巴细胞。采用秩和检验、卡方检验、Kaplan‒Meier曲线和Cox回归模型确定外周血淋巴细胞亚群百分比变化与临床病理特征、临床疗效、无进展生存期(PFS)和总生存期(OS)之间的关系。
ICI治疗后,CD3 + CD8 + T细胞百分比升高,B细胞百分比降低。记忆T细胞百分比的变化因不同免疫疗效组而异。年龄、乙型肝炎感染史、一线治疗和远处转移影响晚期HCC患者外周血淋巴细胞亚群的比例。此外,单因素分析表明,自然杀伤(NK)细胞百分比变化的高百分比变化预测更长的PFS和OS。
ICI治疗改变了接受免疫治疗的HCC患者外周血淋巴细胞亚群的百分比。淋巴细胞亚群比例的变化受免疫反应差异和临床病理特征的影响。在接受ICI治疗的HCC患者中,NK细胞百分比变化的高程度代表独立的预后预测因子。
Background: Immune checkpoint inhibitor (ICI) treatments are promising therapies for hepatocellular carcinoma (HCC) patients.
However, not all HCC patients benefit from immunotherapy. Therefore, it is urgent to explore markers for the clinical efficacy and prognosis of immunotherapy for liver cancer.
This study aimed to investigate changes in peripheral blood lymphocyte subsets after immunotherapy and to assess their predictive and prognostic value. Methods: Sixty-one patients with advanced HCC were enrolled. Peripheral blood samples were collected from HCC patients before and after ICI treatment, and lymphocytes were detected by flow cytometry. The rank sum test, chi-square test, Kaplan‒Meier curve, and Cox regression model were used to determine the relationship between the changes in the percentages of peripheral blood lymphocyte subsets and clinicopathological characteristics, clinical efficacy, progression-free survival (PFS) and overall survival (OS).
Results: After ICI treatment, the percentage of CD3 + CD8 + T cells increased, and the percentage of B cells decreased. The changes in memory T cells percentages varied according to different immune efficacy groups. Age, history of hepatitis B infection, first-line therapy, and distant metastasis influenced the proportion of peripheral blood lymphocyte subsets in patients with advanced HCC.
Furthermore, univariate analysis demonstrated that high percentage changes in the natural killer (NK) cells percentage change predicted longer PFS and OS. Conclusions: ICI treatment alters the percentage of peripheral blood lymphocyte subsets in immunotherapy-treated HCC patients. Changes in the proportion of lymphocyte subsets are influenced by variances in immunological response and clinicopathological features. A high degree of NK cells percentage change in HCC patients treated with ICI represents an independent prognostic predictor.
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