Assessment of PD-L1 Expression on Circulating Tumor Cells for Predicting Clinical Outcomes in Patients with Cancer Receiving PD-1/PD-L1 Blockade Therapies
Assessment of PD-L1 Expression on Circulating Tumor Cells for Predicting Clinical Outcomes in Patients with Cancer Receiving PD-1/PD-L1 Blockade Therapies
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DOI：
10.1002/onco.13981
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发表时间：
2021-09-28
期刊：
影响因子：
5.8
通讯作者：
Xu, Jianming
中科院分区：
文献类型：
--
作者：
Tan, Zhaoli;Yue, Chunyan;Xu, Jianming
背景程序性死亡-1（PD-1）和程序性死亡配体1（PD-L1）阻断免疫疗法改变了癌症治疗的前景。然而，这些疗法的主要局限性是缺乏明确的预测性生物标志物来预测治疗反应。循环肿瘤细胞（CTC）上的PD-L1表达是否与免疫治疗的临床结果相关仍有待广泛研究。材料与方法155例不同类型的晚期肿瘤患者接受抗PD-1/PD-L1单克隆抗体治疗。使用Pep@ MNP方法，分离并计数CTC。通过免疫荧光试验分析PD-L1表达水平，进行半定量评估，分为4类（阴性、低、中和高）。结果免疫治疗前，81.93%（127/155）的患者存在PD-L1阳性CTC，71.61%（111/155）的患者存在至少一种PD-L1高表达CTC。PD-L1阳性CTC组的疾病控制率（DCR）较高（71.56%，91/127），其余个体的DCR仅为39.29%（11/28）（p = .001）。PD-L1高水平患者的客观缓解率和DCR高于其他患者（分别为32.44% vs. 13.64%，p = 0.018和75.68% vs. 40.91%，p <0.0001）。PD-L1阳性CTC和PD-L1高水平CTC的计数和比率降低反映了对PD-1/PD-L1抑制剂的有益应答。此外，PD-L1高CTC患者的无进展生存期（4.9 vs. 2.2个月，p <0.0001）和总生存期（16.1 vs. 9.0个月，p = 0.0235）显著长于无PD-L1高CTC患者。结论CTCs表面PD-L1水平可作为临床免疫治疗的生物标志物，其动态变化可预测治疗效果。本研究旨在研究循环肿瘤细胞上程序性死亡配体1（PD-L1）表达在预测和监测晚期癌症患者对程序性死亡-1（PD-1）/PD-L1阻断免疫疗法的反应中的作用。研究结果表明，PD-L1高表达循环肿瘤细胞（CTC）既是一种预测性生物标志物，也是接受抗PD-1/PD-L1单克隆抗体治疗的晚期癌症患者的预后因素。这些观察结果表明，CTC上的PD-L1水平是免疫治疗的潜在临床生物标志物。
Background Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade immunotherapies have changed the landscape of cancer therapy. However, the main limitation of these therapies is the lack of definitively predictive biomarkers to predict treatment response. Whether PD-L1 expression on circulating tumor cells (CTCs) is associated with the clinical outcomes of immunotherapy remains to be extensively investigated. Materials and Methods One hundred fifty-five patients with different advanced cancers were enrolled in this study and treated with anti-PD-1/PD-L1 monoclonal antibodies. Using the Pep@MNPs method, CTCs were isolated and enumerated. The PD-L1 expression levels were analyzed by an immunofluorescence assay for semiquantitative assessment with four categories (negative, low, medium, and high). Results Prior to immunotherapy, 81.93% (127/155) of patients had PD-L1-positive CTCs, and 71.61% (111/155) had at least one PD-L1-high CTC. The group with PD-L1-positive CTCs had a higher disease control rate (DCR) (71.56%, 91/127), with a DCR of only 39.29% (11/28) for the remaining individuals (p = .001). The objective response rate and DCR in PD-L1-high patients were higher than those in the other patients (32.44% vs. 13.64%, p = .018 and 75.68% vs. 40.91%, p < .0001, respectively). The reduction in the counts and ratios of PD-L1-positive CTCs and PD-L1-high CTCs reflected a beneficial response to PD-1/PD-L1 inhibitors. Furthermore, patients with PD-L1-high CTCs had significantly longer progression-free survival (4.9 vs. 2.2 months, p < .0001) and overall survival (16.1 vs. 9.0 months, p = .0235) than those without PD-L1-high CTCs. Conclusion The PD-L1 level on CTCs may serve as a clinically actionable biomarker for immunotherapy, and its dynamic changes could predict the therapeutic response. Implications for Practice This study was designed to investigate the role of programmed death-ligand 1 (PD-L1) expression on circulating tumor cells in predicting and monitoring response to programmed death-1 (PD-1)/PD-L1 blockade immunotherapies in patients with advanced cancer. The results of the study showed that PD-L1-high-expression circulating tumor cells (CTCs) were both a predictive biomarker and a prognostic factor in patients with advanced cancer treated with anti-PD-1/PD-L1 monoclonal antibodies. These observations suggest that PD-L1 level on CTCs is a potential clinical biomarker for immunotherapy.