Poma Anello Marcello, Bruno Rossella, Pietrini Iacopo, Alì Greta, Pasquini Giulia, Proietti Agnese, Vasile Enrico, Cappelli Sabrina, Chella Antonio, Fontanini Gabriella
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, via Savi 10, 56126 Pisa, Italy.
Unit of Pathological Anatomy, University Hospital of Pisa, via Roma 67, 56126 Pisa, Italy.
Cancers (Basel). 2021 Jul 29;13(15):3828. doi: 10.3390/cancers13153828.
Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, , and showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients' selection for pembrolizumab treatment.
帕博利珠单抗已被批准作为一线治疗药物，用于治疗肿瘤表达程序性死亡受体配体1（PD-L1）且不存在其他可靶向改变的晚期非小细胞肺癌（NSCLC）患者。然而，并非所有符合这些标准的患者都能获得持久益处。在这项单中心研究中，我们旨在根据免疫基因的表达优化患者的选择。纳入了46例一线接受帕博利珠单抗治疗的连续晚期NSCLC患者。通过nanoString系统分析了770个参与免疫系统调节的基因的表达水平。通过免疫组织化学评估PD-L1表达。具有持久临床获益的患者具有更多的细胞毒性细胞、耗竭性CD8、B细胞、CD45、T细胞、CD8 T细胞和自然杀伤（NK）细胞浸润。CD8 T细胞和NK细胞等免疫细胞评分是持久反应的良好预测指标，曲线下面积（AUC）为0.82。在免疫细胞标志物中， 在预测帕博利珠单抗的持久获益方面表现更佳，AUC为0.85。此外， 、 和 在识别对治疗反应良好的患者方面具有高特异性（>0.86）。在同一组患者中，PD-L1表达水平的AUC为0.61。即使使用单一标志物，肿瘤微环境的特征化也可以改善帕博利珠单抗治疗患者的选择。
