NK 细胞活性和甲基化 HOXA9 ctDNA 作为 PD-1/PD-L1 抑制剂治疗非小细胞肺癌患者的预后生物标志物。
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.
机构信息
Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark.
Department of Regional Health Research, University of Southern Denmark, J.B. Winsloews Vej 19, 3rd floor, 5000, Odense C, Denmark.
出版信息
Br J Cancer. 2023 Jul;129(1):135-142. doi: 10.1038/s41416-023-02285-z. Epub 2023 May 3.
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 (IFNγ) 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 IFNγ < 250 pg/ml and detectable ctDNA (n = 27), group 2 consisted of patients with either low levels of IFNγ and undetectable ctDNA or high levels of IFNγ and detectable ctDNA (n = 29), group 3 had IFNγ ≥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.
背景
PD-1/PD-L1 抑制剂改善了非小细胞肺癌（NSCLC）患者的生存。我们评估了自然杀伤细胞活性（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
前瞻性收集 71 例 NSCLC 患者在接受 PD-1/PD-L1 抑制剂治疗前和第 2-4 周期前的血浆。我们使用 NK Vue 测定法测量干扰素 γ（IFNγ）作为 NKA 的替代物。通过液滴数字 PCR 测量甲基化 HOXA9。
结果
一个结合治疗一个周期后 NKA 和 ctDNA 状态的评分具有很强的预后影响。第 1 组 IFNγ<250pg/ml 且检测到 ctDNA（n=27），第 2 组由 IFNγ 水平低且未检测到 ctDNA 或 IFNγ 水平高且检测到 ctDNA 的患者组成（n=29），第 3 组 IFNγ≥250pg/ml 且未检测到 ctDNA（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 组预后不良，风险比为 5.560（95%CI 2.359-13.101，n=71，P<0.001），调整 PD-L1 状态、组织学和表现状态。
结论
在接受 PD-1/PD-L1 抑制剂治疗的 NSCLC 患者中，一个周期后 NKA 和 ctDNA 状态的结合具有预后价值。
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