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:Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer.
Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer.
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研究结果表明,免疫细胞亚群和表型,特别是 Treg 细胞、HLA-DR + CD4 + T 细胞和 naïve CD4 + T 细胞,在评估肺癌患者短期 PD-1/PD-L1 治疗疗效方面可能具有预测作用。这些见解为个性化治疗策略提供了有价值的前景,并强调了免疫分析在肺癌免疫治疗中的重要性。
免疫检查点抑制剂,如抗程序性细胞死亡-1(PD-1)和PD-1配体-1(PD-L1)抗体,在提高肺癌长期生存率方面取得了突破性成果。尽管高水平的PD-L1表达和肿瘤突变负荷已成为关键生物标志物,但并非所有患者都能获得持久获益,免疫检查点阻断耐药仍是一个普遍问题。理解肺癌的免疫学复杂性对于揭示调控免疫调节治疗应答和耐药的机制至关重要。本研究旨在探索外周免疫标志物在预测接受PD-1/PD-L1检查点抑制剂治疗的肺癌患者治疗效率方面的潜力。
本研究纳入71例接受PD-1/PD-L1抑制剂治疗的肺癌患者和20例健康对照。检测了免疫细胞亚群(CD4+ T细胞、CD8+ T细胞、B细胞、NK细胞和NKT细胞)、T细胞和B细胞的表型分析,以及PMA/Ionomycin刺激的淋巴细胞功能试验。
肺癌患者的免疫细胞亚群出现显著改变,尤其是Treg细胞比例升高。治疗后,CD3+ T细胞、CD8+ T细胞和NKT细胞的绝对数量大幅增加,同时CD3+ T细胞和CD8+ T细胞上HLA-DR表达增强。完全缓解组与非完全缓解(NCR)组比较显示,NCR组Treg细胞比例和HLA-DR+ CD4+ T细胞更高。
Immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) antibodies, have achieved breakthrough results in improving long-term survival rates in lung cancer. Although high levels of PD-L1 expression and tumor mutational burden have emerged as pivotal biomarkers, not all patients derive lasting benefits, and resistance to immune checkpoint blockade remains a prevalent issue. Comprehending the immunological intricacies of lung cancer is crucial for uncovering the mechanisms that govern responses and resistance to immunomodulatory treatments. This study aimed to explore the potential of peripheral immune markers in predicting treatment efficiency among lung cancer patients undergoing PD-1/PD-L1 checkpoint inhibitors.
This study enrolled 71 lung cancer patients undergoing PD-1/PD-L1 inhibitor therapy and 20 healthy controls. Immune cell subsets (CD4 + T cells, CD8 + T cells, B cells, NK cells, and NKT cells), phenotypic analysis of T cells and B cells, and PMA/Ionomycin-stimulated lymphocyte function assay were conducted.
Lung cancer patients exhibited significant alterations in immune cell subsets, notably an increased percentage of Treg cells. Post-treatment, there were substantial increases in absolute numbers of CD3 + T cells, CD8 + T cells, and NKT cells, along with heightened HLA-DR expression on CD3 + T and CD8 + T cells. Comparison between complete remission and non-complete remission (NCR) groups showed higher Treg cell percentages and HLA-DR + CD4 + T cells in the NCR group.
The study findings suggest potential predictive roles for immune cell subsets and phenotypes, particularly Treg cells, HLA-DR + CD4 + T cells, and naïve CD4 + T cells, in evaluating short-term PD-1/PD-L1 therapy efficacy for lung cancer patients. These insights offer valuable prospects for personalized treatment strategies and underscore the importance of immune profiling in lung cancer immunotherapy.
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