质谱细胞术揭示了与肺癌患者接受派姆单抗治疗疗效相关的经典单核细胞、NK 细胞和 ICOS+CD4+T 细胞。

Mass Cytometry Reveals Classical Monocytes, NK Cells, and ICOS+ CD4+ T Cells Associated with Pembrolizumab Efficacy in Patients with Lung Cancer.

机构信息

Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California.

Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France.

出版信息

Clin Cancer Res. 2022 Dec 1;28(23):5136-5148. doi: 10.1158/1078-0432.CCR-22-1386.

PURPOSE

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of non-small cell lung cancer (NSCLC), but predictive biomarkers of their efficacy are imperfect. The primary objective is to evaluate circulating immune predictors of pembrolizumab efficacy in patients with advanced NSCLC.

EXPERIMENTAL DESIGN

We used high-dimensional mass cytometry (CyTOF) in baseline blood samples of patients with advanced NSCLC treated with pembrolizumab. CyTOF data were analyzed by machine-learning algorithms (Citrus, tSNE) and confirmed by manual gating followed by principal component analysis (between-group analysis).

RESULTS

We analyzed 27 patients from the seminal KEYNOTE-001 study (median follow-up of 60.6 months). We demonstrate that blood baseline frequencies of classical monocytes, natural killer (NK) cells, and ICOS+ CD4+ T cells are significantly associated with improved objective response rates, progression-free survival, and overall survival (OS). In addition, we report that a baseline immune peripheral score combining these three populations strongly predicts pembrolizumab efficacy (OS: HR = 0.25; 95% confidence interval = 0.12-0.51; P < 0.0001).

CONCLUSIONS

As this immune monitoring is easy in routine practice, we anticipate our findings may improve prediction of ICI benefit in patients with advanced NSCLC.

目的

免疫检查点抑制剂（ICI）彻底改变了非小细胞肺癌（NSCLC）的治疗方法，但它们疗效的预测生物标志物并不完善。主要目的是评估循环免疫预测因子对接受派姆单抗治疗的晚期 NSCLC 患者的疗效。

实验设计

我们在接受派姆单抗治疗的晚期 NSCLC 患者的基线血液样本中使用了高维质谱流式细胞术（CyTOF）。通过机器学习算法（Citrus、tSNE）对 CyTOF 数据进行分析，并通过手动门控和主成分分析（组间分析）进行验证。

结果

我们分析了来自关键性 KEYNOTE-001 研究的 27 例患者（中位随访 60.6 个月）。我们证明，经典单核细胞、自然杀伤（NK）细胞和 ICOS+CD4+T 细胞的基线血液频率与客观缓解率、无进展生存期和总生存期（OS）的改善显著相关。此外，我们报告称，结合这三种细胞群的基线免疫外周评分强烈预测派姆单抗的疗效（OS：HR=0.25；95%置信区间=0.12-0.51；P<0.0001）。