Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.
Breast Cancer Res Treat. 2023 Jul;200(2):281-291. doi: 10.1007/s10549-023-06972-6. Epub 2023 May 25.
Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predicting and stratifying metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy.
Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high).
Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P = 0.033) and OS (P = 0.00058) compared with patients with a cut-off value of < 35% PD-L1-high CTCs.
Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy.
乳腺癌已成为女性癌症死亡的主要原因。虽然针对程序性死亡受体-1（PD-1）的免疫检查点抑制剂具有广阔的前景，但目前尚不清楚循环肿瘤细胞（CTC）上的 PD-L1 表达是否具有预测和分层转移性乳腺癌（MBC）患者的价值，这些患者可以从抗 PD-1 免疫治疗中获益。
本研究纳入了 26 名接受抗 PD-1 免疫治疗的 MBC 患者。使用基于肽的 Pep@MNPs 方法从 2.0ml 外周静脉血中分离和计数 CTCs。通过建立的免疫评分系统将 PD-L1 在 CTCs 上的表达评估为四个类别（阴性、低、中、高）。
我们的数据显示，92.3%（24/26）的患者有 CTCs，83.3%（20/26）的患者有 PD-L1 阳性 CTCs，65.4%（17/26）的患者有 PD-L1 高 CTCs。我们发现，PD-L1 高 CTCs 截断值≥35%的患者的临床获益率（CBR）（66.6%）高于其他患者（29.4%）。我们表明，接受抗 PD-1 单药治疗的 MBC 患者的 CTCs 上的 PD-L1 表达是动态的。我们证明，PD-L1 高 CTCs 截断值≥35%的 MBC 患者的 PFS（P=0.033）和 OS（P=0.00058）长于 PD-L1 高 CTCs 截断值<35%的患者。
我们的研究结果表明，CTC 上的 PD-L1 表达可以预测治疗反应和临床结局，为接受抗 PD-1 免疫治疗的患者提供了有价值的预测和预后生物标志物。
