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
NK 细胞活性与甲基化 HOXA9 ctDNA 作为接受 PD-1/PD-L1 抑制剂治疗的非小细胞肺癌患者的预后生物标志物
英文原题：NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.
查看英文原题
NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.
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研究概要
在 NSCLC 患者接受 PD-1/PD-L1 抑制剂治疗后，一个周期治疗后结合 NKA 和 ctDNA 状态具有预后价值。
研究思路结论见上方概要
背景
PD-1/PD-L1抑制剂改善了非小细胞肺癌（NSCLC）患者的生存。我们评估了NK 细胞活性（NKA）和甲基化HOXA9循环肿瘤DNA（ctDNA）作为接受PD-1/PD-L1抑制剂治疗的NSCLC患者的预后生物标志物。
方法
血浆前瞻性采集自71例NSCLC患者，分别在PD-1/PD-L1抑制剂治疗前以及第2-4周期前采集。我们使用NK Vue检测法测定干扰素γ（IFN）水平，作为NKA的替代指标。甲基化HOXA9通过微滴数字PCR检测。
结果
一个治疗周期后测量的结合 NKA 和 ctDNA 状态的评分具有强烈的预后影响。第1组 IFN < 250 pg/ml 且 ctDNA 可检测到（n = 27），第2组由 IFN 低水平且 ctDNA 不可检测到或 IFN 高水平且 ctDNA 可检测到的患者组成（n = 29），第3组 IFN 250 pg/ml 且 ctDNA 不可检测到（n = 15）。中位 OS 分别为 221 天（95% CI 121-539 天）、419 天（95% CI 235-650 天）和 1158 天（95% CI 250 天-未达到）（P = 0.002）。第1组预后差，调整 PD-L1 状态、组织学和体能状态后，风险比为 5.560（95% CI 2.359-13.101，n = 71，P < 0.001）。
展开英文摘要原文
BACKGROUND
PD-1/PD-L1 inhibitors have improved survival for patients with non-small cell lung cancer (NSCLC). We evaluated natural killer cell activity (NKA) and methylated HOXA9 circulating tumor DNA (ctDNA) as prognostic biomarkers in NSCLC patients treated with PD-1/PD-L1 inhibitors.
METHODS
Plasma was prospectively collected from 71 NSCLC patients before treatment with PD-1/PD-L1 inhibitors and before cycles 2-4. We used the NK Vue assay to measure the level of interferon gamma (IFN ) as a surrogate for NKA. Methylated HOXA9 was measured by droplet digital PCR.
RESULTS
A score combining NKA and ctDNA status measured after one treatment cycle had a strong prognostic impact. Group 1 had IFN < 250 pg/ml and detectable ctDNA (n = 27), group 2 consisted of patients with either low levels of IFN and undetectable ctDNA or high levels of IFN and detectable ctDNA (n = 29), group 3 had IFN 250 pg/ml and undetectable ctDNA (n = 15). Median OS was 221 days (95% CI 121-539 days), 419 days (95% CI 235-650 days), and 1158 days (95% CI 250 days-not reached), respectively (P = 0.002). Group 1 had a poor prognosis with a hazard ratio of 5.560 (95% CI 2.359-13.101, n = 71, P < 0.001) adjusting for PD-L1 status, histology, and performance status.
CONCLUSIONS
Combining NKA and ctDNA status after one cycle of treatment was prognostic in patients with NSCLC treated with PD-1/PD-L1 inhibitors.
论文信息
- 作者
- Wen SWC、Nederby L、Andersen RF、Hansen TS、Nyhus CH、Hilberg O、Jakobsen A、Hansen TF
- 单位
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark. sara.witting.christensen.wen@rsyd.dk.Denmark
- 文献类型
- 非美国政府资助研究
- 期刊
- British journal of cancer2023 Jul
- 原文标识
- PubMed 37137997 · DOI 10.1038/s41416-023-02285-z
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