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:Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.
Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.
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免疫检查点抑制剂改变了免疫治疗反应良好患者外周血淋巴细胞亚群的比例。不同淋巴细胞亚群的水平可作为接受免疫治疗的 NSCLC 患者疗效和临床预后的有价值预测生物标志物。
免疫检查点抑制剂(ICIs)在非小细胞肺癌(NSCLC)患者中取得了令人鼓舞的疗效。然而,并非所有NSCLC患者都能从免疫治疗中获益。目前迫切需要探索能够预测接受免疫治疗的晚期NSCLC患者生存结局和治疗疗效的生物标志物。在本研究中,我们旨在评估外周血淋巴细胞亚群的变化及其与接受免疫治疗的晚期NSCLC患者治疗疗效和临床预后之间的关联。
共纳入276例晚期NSCLC患者。在未接受任何治疗前、免疫治疗或化疗前,以及免疫治疗或化疗4个周期后,采集外周血淋巴细胞亚群,包括CD4 + T细胞、CD8 + T细胞、CD4 + /CD8 + 比值、NK细胞、Tregs和B细胞。采用T检验分析影响淋巴细胞亚群的因素及其治疗前后的变化。采用Logistic回归绘制ROC曲线并分析淋巴细胞亚群与疗效的关系。采用Log-rank检验和Cox回归模型评估淋巴细胞亚群与无进展生存期(PFS)的关系。
性别、远处转移和 EGFR 突变状态已知会影响晚期 NSCLC 患者外周血淋巴细胞亚群的比例。与基线相比,化疗后 CD4 + T 细胞、CD8 + T 细胞、Tregs 和 B 细胞的比例下降。免疫治疗后 CD4 + T 细胞、CD8 + T 细胞、CD4 + /CD8 + 比值、NK 细胞和 Tregs 的比例高于化疗后。与基线相比,有效组在 4 个周期免疫治疗后外周血中 CD4 + T 细胞、CD4 + /CD8 + 比值、NK 细胞和 Tregs 的比例显著升高,CD8 + T 细胞数量显著降低。相反,无效组在上述参数中未显示任何显著差异。基线 CD4 + T 细胞和 NK 细胞是免疫治疗疗效和 PFS 的独立预测因素。基线 Tregs 是免疫治疗疗效的独立预测因素。
Immune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy.
A total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4 + T cells, CD8 + T cells, CD4 + /CD8 + ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS).
Gender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4 + T cells, CD8 + T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4 + T cells, CD8 + T cells, CD4 + /CD8 + ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4 + T cells, CD4 + /CD8 + ratio, NK cells and Tregs, and the number of CD8 + T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4 + T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy.
Immune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.
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