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:Peripheral CD4(+) T cells correlate with response and survival in patients with advanced non-small cell lung cancer receiving chemo-immunotherapy.
Peripheral CD4(+) T cells correlate with response and survival in patients with advanced non-small cell lung cancer receiving chemo-immunotherapy.
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我们的发现揭示了高 CD4+/总 T 细胞比率与良好的反应和预后相关,突显了其作为预测性生物标志物指导选择可能对铂类和抗 PD-1 联合治疗有反应者的潜力。
本研究旨在探讨外周免疫细胞在预测接受抗PD-1免疫治疗联合铂类化疗的晚期非小细胞肺癌(NSCLC)患者疗效和预后方面的潜力。对象与方法:我们采用流式细胞术检测了2019年12月至2022年1月期间接受化学免疫治疗的79例晚期NSCLC患者血液免疫细胞的水平及动态变化。治疗前和治疗后血样分别于联合治疗第一周期和第三周期开始前3天内采集。采用Kaplan-Meier法和Cox回归模型进行无进展生存期(PFS)和总生存期(OS)分析。
治疗前CD4+/总T细胞比值在缓解者中显著高于非缓解者(P < 0.05)。治疗前总淋巴细胞(P = 0.012)、总B淋巴细胞(P = 0.025)和NK细胞(P = 0.022)水平,以及治疗后NK细胞(P = 0.011)和NKT细胞(P = 0.035)水平与OS显著相关。治疗后CD8+/总T细胞比值与OS呈正相关(P = 0.038)。在多因素分析中,治疗后NK细胞和治疗后CD4+CD8+/总T细胞比值分别与OS(风险比[HR] = 10.30,P = 0.038)和PFS(HR = 1.95,P = 0.022)呈负相关。值得注意的是,CD4+/总T细胞比值与预后在治疗前后均呈显著正相关(P < 0.05)。
The aim of the present study was to explore the potential of peripheral immune cells in predicting the response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1 immunotherapy and platinum-based chemotherapy. PARTICIPANTS AND METHODS: We utilized flow cytometry to examine the levels and dynamics of blood immune cells in 79 advanced NSCLC patients treated with the chemoimmunotherapy between December 2019 and January 2022. The pre- and post-treatment blood samples were collected within 3 days prior to the initiation of the first and third cycle of combination treatment, respectively. Progression-free survival (PFS) and overall survival (OS) analyses were conducted using Kaplan-Meier method and Cox regression models.
The pre-treatment CD4 + /Total T cells ratio was significantly higher in responders than non-responders ( P < 0.05). The levels of pre-treatment total lymphocytes ( P = 0.012), total B lymphocytes ( P = 0.025), and NK cells ( P = 0.022), and post-treatment NK cells ( P = 0.011) and NKT cells ( P = 0.035) were significantly associated with OS. Post-treatment CD8 + /Total T cells ratio was positively correlated with OS ( P = 0.038). In multivariate analysis, post-treatment NK cells and post-treatment CD4 + CD8 + /Total T cells ratio were negatively associated with OS (hazard ratio [HR] = 10.30, P = 0.038) and PFS (HR = 1.95, P = 0.022), respectively. Notably, significantly positive correlations were observed between CD4 + /Total T cells ratio and prognosis both before and after treatment ( P < 0.05).
To summarize, our finding reveals that high CD4 + /total T cells ratio was associated with favorable response and prognosis, highlighting its potential as a predictive biomarker to guide the selection of likely responders to platinum and anti-PD-1 combination therapy.
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