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 the efficacy and prognosis of PD‑1 inhibitor therapy in advanced gastric cancer: results from a monocentric retrospective study.
Association of lymphocyte subsets with the efficacy and prognosis of PD‑1 inhibitor therapy in advanced gastric cancer: results from a monocentric retrospective study.
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外周血淋巴细胞亚群的比例在对 PD-1 抑制剂有应答的患者中发生了改变。不同的淋巴细胞亚群水平可作为生物标志物,用于预测晚期胃癌患者的免疫治疗疗效和临床预后。
这项回顾性研究旨在探讨晚期胃癌患者免疫治疗前后外周血淋巴细胞亚群的变化及其与疗效和临床预后的关系。
收集2020年1月至2021年10月于山西医科大学第一医院接受免疫治疗的195例晚期胃癌患者的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、Treg细胞和B细胞,分别在晚期胃癌确诊时、免疫治疗前和免疫治疗3个周期后采集。采用t检验分析患者外周血淋巴细胞亚群的影响因素及免疫治疗后的变化。为探讨淋巴细胞亚群与治疗结局的关系,采用logistic回归绘制ROC曲线。绘制Kaplan-Meier曲线,并进行Log Rank检验,比较不同组间PFS的差异。在校正其他变量后,采用Cox比例风险回归模型分析影响PFS的因素。
晚期胃癌患者外周血淋巴细胞亚群的比例受年龄和PD-L1水平影响。与基线相比,治疗有效组在免疫治疗三个周期后外周血中CD4+T细胞比例、CD4+/CD8+比值、NK细胞和Treg细胞比例较高,而CD8+T细胞和B细胞比例较低。在初治组中,淋巴细胞亚群无显著差异。以30.60%和18.00%为截断值,基线CD4+T细胞和NK细胞比例为免疫治疗疗效和PFS的独立预测因素。Treg细胞比例、性别、PD-L1水平和MMR状态均独立预测PFS。
This retrospective study aimed to investigate the changes in peripheral blood lymphocyte subsets before and after immunotherapy in patients with advanced gastric cancer and their relationship n with the therapeutic efficacy and clinical prognosis.
Peripheral blood lymphocyte subsets, including CD4 + T cells, CD8 + T cells, CD4+/CD8 + ratio, NK cells, Treg cells, and B cells, were collected from 195 patients with advanced gastric cancer who were admitted to the First Hospital of Shanxi Medical University with immunotherapy from January 2020 to October 2021, at the time of diagnosis of advanced gastric cancer, before immunotherapy and after 3 cycles of immunotherapy. T-tests were used to examine the factors influencing the patients' peripheral blood lymphocyte subsets and the changes after immunotherapy. To examine the relationship between lymphocyte subsets and treatment outcomes, ROC curves were plotted using a logistic regression. Kaplan-Meier curve was drawn, and the Log Rank test was carried out to compare the differences in PFS between the different groups. Cox proportional hazards regression model was used to analyze the factors affecting PFS after calibration of other variables.
The proportion of peripheral blood lymphocyte subsets in patients with advanced gastric cancer was affected by age and PD-L1 level. Compared to the baseline, the treatment effective group had higher proportions of CD4 + T cells, a higher CD4+/CD8 + ratio, NK cells and Treg cells, and lower proportions of CD8 + T cells and B cells in the peripheral blood after three cycles of immunotherapy. In the treatment-naive group, there were no significant differences in the lymphocyte subsets. With cut-off values of 30.60% and 18.00%, baseline CD4 + T cell and NK cell ratios were independent predictors of immunotherapy efficacy and PFS. Treg cell ratio, gender, PD-L1 levels, and MMR status all predicted PFS independently.
The proportion of peripheral blood lymphocyte subsets was modified in patients who responded to PD-1 inhibitors. Different lymphocyte subpopulation levels can be used as biomarkers to predict immunotherapy efficacy and clinical prognosis in patients with advanced gastric cancer.
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